Notes

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Furthermore 125I seed radiation induced increased production of reactive oxygen species (ROS) in both ESCC cell lines. Treatment with an ROS scavenger significantly attenuated the effects of 125I seed radiation on endoplasmic reticulum stress, autophagy, apoptosis, paraptotic vacuoles and reduced cell viability. In vivo experiments showed that 125I seed brachytherapy induced ROS generation, initiated cell apoptosis and potential paraptosis, and inhibited cell proliferation and tumor growth. In summary, the results demonstrate that in ESCC cells, 125I seed radiation induces cell death through both apoptosis and paraptosis; and at the same time initiates protective autophagy. Additionally, 125I seed radiation‑induced apoptosis, paraptosis and autophagy was considerably mediated by ROS.There is extensive evidence suggesting that microRNAs (miRs) can modulate the activity of oncogenes and tumor suppressors, and are associated with the occurrence of cancer. In the present study, the function of miR‑363‑3p in the progression of retinoblastoma (RB) was investigated. miR‑363‑3p expression in RB was decreased, and miR‑363‑3p protein levels were found to be inversely correlated with phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α (PIK3CA) levels. Overexpression of miR‑363‑3p in an in vitro model of RB revealed that miR‑363‑3p had anticancer effects on RB and regulated PIK3CA, pyruvate dehydrogenase kinase 1 (PDK1) and phosphorylated protein kinase B (p‑AKT) protein expression. Downregulation of miR‑363‑3p promoted cell proliferation of RB cells through PIK3CA, PDK1 and p‑AKT protein expression. Knockdown of PIK3CA increased the anticancer effects of miR‑363‑3p in RB cells. Treatment with OSU‑03012, a PDK1 inhibitor, accelerated the anticancer effects of miR‑363‑3p in RB cells. Taken together, the results demonstrate that miR‑363‑3p functions as a tumor suppressor in RB by targeting PIK3CA.Glioblastoma is a malignant brain tumor exhibiting highly aggressive proliferation and invasion capacities. Despite treatment by aggressive surgical resection and adjuvant therapy including temozolomide and radiation therapy, patient prognosis remains poor. Lenalidomide, a derivative of thalidomide, is known to be an immunomodulatory agent that has been used to treat hematopoietic malignancies. There are numerous studies revealing an antitumor effect of lenalidomide in hematopoietic cells, but not in glioma cells. The present study aimed to demonstrate the antitumor effect of lenalidomide on malignant glioma cell lines. The growth inhibition of malignant glioma cells (A‑172, AM‑38, T98G, U‑138MG, U‑251MG, and YH‑13) by lenalidomide was assessed using a Coulter counter. The mechanism of the antitumor effect of lenalidomide was examined employing a fluorescence‑activated cell sorter, western blot analysis, and quantitative real‑time reverse transcriptional polymerase chain reaction (RT‑qPCR) in malignant glioma cell lines (A‑172, AM‑38). The results revealed that the number of malignant glioma cells was decreased in a concentration‑dependent manner by lenalidomide. DNA flow cytometric analysis demonstrated an increase in the ratio of cells at the G0/G1 phase following lenalidomide treatment. Western blot analysis and RT‑qPCR revealed that p53 activation and the expression of p21 were increased in glioma cells treated with lenalidomide. Western blot analysis revealed that cleavage of PARP did not occur; however, increased expression of Bax protein, cleavage of caspase‑9 and cleavage of caspase‑3 were confirmed. Analysis by FACS also supported the conclusion that little apoptosis induction occurred following lenalidomide treatment of malignant glioma cell lines. In conclusion, lenalidomide exerts an antitumor effect on glioma cells due to alterations in cell cycle distribution.Scutellaria baicalensis (S. baicalensis) is a plant that is widely used for medicinal purposes. Baicalein, one of the primary bioactive compounds found in S. baicalensis, is thought to possess antitumor activity, although the specific mechanisms remain unclear. Therefore, the present study aimed to evaluate the ability of baicalein to disrupt the proliferation and metastatic potential of colorectal cancer (CRC) cells; a rapid and sensitive ultra‑high performance liquid chromatography‑tandem mass spectrometric method was employed for the identification of baicalein in an S. baicalensis aqueous extract and in rat plasma. To investigate the effects of baicalein, Cell Counting Kit‑8 (CCK‑8), western blotting, wound‑healing and Transwell assays were performed. The data indicated that baicalein was absorbed into the blood and was able to effectively disrupt the proliferation, migration and invasion abilities of CRC cells in a dose‑ and time‑dependent manner. Baicalein treatment was also revealed to decrease the expression of epithelial‑mesenchymal transition (EMT)‑promoting factors including vimentin, Twist1, and Snail, but to upregulate the expression of E‑cadherin in CRC cells. The expression levels of cell cycle inhibitory proteins p53 and p21 also increased following baicalein treatment. In addition, Snail‑induced vimentin and Twist1 upregulation, as well as E‑cadherin downregulation, were reversed following treatment with baicalein. In conclusion, the results of the present study indicate that baicalein may suppress EMT, at least in part, by decreasing Snail activity.TEA Domain Transcription Factors (TEADs) are important in development and serve essential roles in tumorigenesis; however, the role of TEAD2 expression in hepatocellular carcinoma (HCC) has not been widely examined. The present study was conducted to investigate the expression status of TEAD2 in HCC and to evaluate whether the expression of TEAD2 is associated with the prognosis of patients with HCC. mRNA expression data was retrieved for Hippo pathway genes of 50 normal control and 377 HCC samples from The Cancer Genome Atlas data portal. Gene set enrichment, GeneNeighbors, ClassNeighbors and survival analyses were then performed based on the gene expression levels. The mRNA expression of TEAD2 and VGLL4 was significantly higher in HCC compared with the normal control samples, and the mRNA expression of TEAD2 was higher in advanced stages than in early stages. Specifically, survival analysis revealed that higher mRNA expression of TEAD2 was significantly associated with a less favorable overall survival rate (P=0.0067) and there was a trend towards significance between higher mRNA expression of VGLL4 and poor overall survival rate (P=0.051). According to the gene set enrichment analysis, patients with higher mRNA expression of TEAD2 and VGLL4 had strongly enhanced epithelial‑mesenchymal transition and angiogenesis, which are associated with tumor progression. In conclusion, increased mRNA expression of TEAD2 is associated with a poor prognosis in patients with HCC. TEAD2 may serve as a prognostic factor for HCC and a novel therapeutic target.The aim of the present study was to investigate the underlying mechanisms of thymus‑expressed chemokine (TECK) autocrine signaling, and its effect on carcinogenesis and the development of breast cancer. The present study also assessed epithelial‑mensenchymal transition (EMT) and cell migration, invasion, proliferation and apoptosis. Breast cancer cell lines MCF‑7 and MDA‑MB‑231 were used in the present study, and TECK basic expression in cancer cells was investigated using western blotting (WB). EMT markers, Akt pathway molecules and apoptosis indicators were detected by reverse transcription‑quantitative PCR or WB. In order to assess migration and invasion, wound healing and Matrigel invasion assays were performed. Moreover, flow cytometry was used to assess the rate of proliferation and apoptosis. In vivo experiments were conducted in nude mice to assess cancer growth. It was revealed that breast cancer cells could secrete TECK in an autocrine manner. Furthermore, TECK could increase cell migration and invasion by promoting EMT and inhibit apoptosis via the Akt signaling pathway.Lysyl oxidase‑like 2 (LOXL2), a member of the lysyl oxidase gene family, is involved in the progression of hepatocellular carcinoma progression and metastasis. Increased expression of LOXL2 has been identified in several types of cancer, including hepatocellular carcinoma. Recently, LOXL2 has been reported to promote epithelial‑mesenchymal transition by reducing E‑cadherin expression via the upregulation of Snail expression. The present study provided evidence demonstrating that LOXL2 inhibited the expression of fructose‑1, 6‑biphosphatase (FBP1) and enhanced the glycolysis of Huh7 and Hep3B hepatocellular carcinoma cell lines in a Snail‑dependent manner. Overexpression of the point‑mutated form of LOXL2 [LOXL2(Y689F)], which lacks enzymatic activity, does not affect the expression of Snail1 or FBP1. Notably, targeting extracellular LOXL2 of Huh7 cells with a therapeutic antibody was unable to abolish its regulation on the expression of Snail and FBP1. Knockdown of LOXL2 also interrupted the angiogenesis of Huh7 and Hep3B cells, and this effect could be rescued by the overexpression of Snail. Furthermore, upregulation of hypoxia‑inducible factor 1α (HIF‑1α) and vascular endothelial growth factor (VEGF) expression was observed in Huh7 and Hep3B cells expressing wild‑type LOXL2. Notably, the selective LOXL2 inhibitor LOXL2‑IN‑1 could upregulate the expression of FBP1 and inhibit the expression of Snail, HIF‑1α and VEGF in HCC cells, but not in FBP1‑knockdown cells. The results of the present study indicated that the intracellular activity of LOXL2 upregulated HIF‑1α/VEGF signaling pathways via the Snail‑FBP1 axis, and this phenomenon could be inhibited by LOXL2 inhibition. Collectively, these findings further support that LOXL2 exhibits an important role in the progression of hepatocellular carcinoma and implicates LOXL2 as a potential therapeutic agent for the treatment of this disease.Knee osteoarthritis (KOA) is a major cause of leg disability in the elderly population. Recently, the expression levels of circulating microRNA (miRNA) let‑7e have been reported to be significantly reduced in KOA. The aims of the present study were to assess the feasibility of let‑7e as a serum marker for detecting KOA and to explore the underlying mechanisms of its involvement. Based on previous studies and bioinformatics analysis, let‑7e may regulate apoptosis and autophagy of articular chondrocytes. A total of 10 patients with KOA and 10 patients with trauma without KOA were recruited to examine the levels of let‑7e in peripheral blood. Subsequently, KOA rat models were established, and the levels of let‑7e in the cartilage and serum were examined, the expression of apoptotic proteins and autophagy‑related proteins in the cartilage were investigated, and apoptotic and autophagic activities of primary cultured chondrocytes were also detected. In patients with KOA, let‑7e levels in the peripheral serum were significantly decreased compared with the control group, and this result was confirmed in the peripheral serum and cartilage of KOA rats. In addition, the expression levels of proteins involved in the apoptotic pathway were increased in the cartilage of KOA rats, and apoptotic activity was increased. The expression of autophagy‑related proteins beclin 1 and microtubule associated protein 1 light chain 3 β (LC3B) II/LC3BI in the articular cartilage of KOA rats was lower compared with the controls, and autophagy was decreased. Si‑Miao‑San (SMS) treatment restored the expression of let‑7e and reversed the changes in apoptosis and autophagy. Therefore, the present study provided additional evidence that circulating let‑7e may be a potential serum biomarker for the diagnosis and treatment of KOA. Elevated apoptosis levels and decreased autophagy levels of cartilage tissue are involved in KOA, and treatment with SMS may reverse these effects.Progressive cardiac conduction defect (PCCD) is an inherited autosomal dominant cardiac disorder characterized by an age‑dependent cardiac electrical conduction block. Several genes have been associated with the genetic pathogenesis of PCCD. The present study aimed to identify the causal mutation of PCCD and to investigate the association between genotype and phenotype in a Chinese family with PCCD. A total of 39 family members were included in the present study. All subjects participated in physical, biochemical, electrocardiography and echocardiography examinations. Whole‑exome sequencing was performed for four individuals from the same generation, including three patients with PCCD and one normal control with no cardiovascular disease. Sanger sequencing and in silico analysis were used to identify the causal mutation. Whole‑exome sequencing and variant identification revealed a candidate nonsense mutation (c.1443C>A, p.Tyr481*) in lamin A/C (LMNA). The mutation was identified in seven patients (including the proband) and two asymptomatic mutation carriers, but it was not detected in 100 control subjects of matched ancestry. Clinical examinations identified typical symptoms in patients with PCCD, including bradycardia and various types of conduction defect, and excluded other phenotypes related to the LMNA mutation. The genotype and phenotype were co‑associated among all participants. In the present study, the c.1443C>A mutation in the LMNA gene was identified as a potential cause of PCCD. In silico analysis predicted that the identified mutation was damaging through its effect on the lamin tail domain of LMNA. From the present study, it could be suggested that genetic screening and family counseling, early pacemaker implantation or a sudden death in the family may be essential for risk stratification and treatment of patients with PCCD.Endometrial adenocarcinoma is one of the most common types of gynecological malignancies and its incidence and mortality rates are increasing. Due to tumor recurrence and metastasis, the overall five‑year survival rate of patients with endometrial adenocarcinoma is shortened. The aim of the present was to investigate the role of the polycomb group protein B‑lymphoma Mo‑MLV insertion region 1 (BMI‑1) in the invasion, metastasis and the epithelial‑mesenchymal transition (EMT) of endometrial adenocarcinoma cells, as well its effects on the prognosis of patients with endometrial adenocarcinoma. Immunohistochemistry was used to examine the expression profile of BMI‑1 in normal and endometrial adenocarcinoma tissues. Western blotting was used to examine the expression levels of BMI‑1 and EMT markers. Kaplan‑Meier plots and a Cox proportional hazards model were used to assess the overall survival. MTT cell viability assays were used to detect the proliferation of endometrial cancer cells. Transwell assays were used xpression levels of the epithelial markers E‑cadherin and keratin, and decreased the expression levels of the mesenchymal markers N‑cadherin, vimentin and the downstream transcription factor, Slug. In conclusion, BMI‑1 expression was correlated with tumor invasion and metastasis, contributing to deep myometrial invasion and lymph node metastasis, and was a poor prognostic factor for endometrial adenocarcinoma.Patient‑derived orthotopic glioma xenograft models are important platforms used for pre‑clinical research of glioma. In the present study, the diagnostic ability of magnetic resonance imaging (MRI) was examined with regard to the identification of biomarkers obtained from patient‑derived glioma xenografts and human tumors. Conventional MRI, diffusion weighted imaging and dynamic contrast‑enhanced (DCE)‑MRI were used to analyze seven pairs of high grade gliomas with their corresponding xenografts obtained from non‑obese diabetic‑severe‑combined immunodeficiency nude mice. Tumor samples were collected for transcriptome sequencing and histopathological staining, and differentially expressed genes were screened between the original tumors and the corresponding xenografts. Gene Ontology (GO) analysis was performed to predict the functions of these genes. In 6 cases of xenografts with diffuse growth, the degree of enhancement was significantly lower compared with the original tumors. Histopathological staining indi different compared with those of the original patient tumors. Differential gene expression may underlie the differences noted in the MRI features between original tumors and corresponding xenografts. The results of the present study highlight the precautions that should be taken when extrapolating data from patient‑derived xenograft studies, and their applicability to humans.CD4+ regulatory T (Treg) cells are associated with immune tolerance and antitumor immunosuppression. The aim of the present study was to investigate the role and molecular mechanism of C‑C motif chemokine ligand 11 (CCL11) in the regulation of Treg cells from patients with breast cancer (BC) and healthy individuals in vitro, and from tumor‑bearing mice in vivo. CD4+ T cells isolated from patients with BC or healthy individuals were incubated with anti‑CCL11 neutralizing antibodies or recombinant human CCL11 protein, in the presence or absence of a STAT5 inhibitor. The serum CCL11 level and proportion of Treg cells characterized as CD4+CD25+forkhead box P3+ (Foxp3) among the CD4+ T cells in patients with BC and healthy individuals were analyzed by ELISA and flow cytometry, respectively. CCL11, C‑C motif chemokine receptor 3 (CCR3), Foxp3, phosphorylated‑STAT5 and STAT5 expression levels were determined by western blotting. The serum CCL11 level and the proportion of CD4+CD25+Foxp3+ Treg cells were significantly increased in patients with BC compared with healthy individuals. CCL11 blockade reduced the proportion of CD4+CD25+Foxp3+ Treg cells, the expression of CCR3 and Foxp3, and the level of STAT5 activation in tumor‑associated CD4+ T cells, in a dose‑dependent manner. CCL11 blockade also reduced the proportion of CD4+CD25+Foxp3+ Treg cells and the serum levels of interleukin (IL)‑2 and transforming growth factor (TGF)‑β1 in tumor‑bearing mice. The recombinant human CCL11 protein increased the proportion of CD4+CD25+Foxp3+ Treg cells, the expression of CCR3 and Foxp3, and the release of IL‑2 and TGF‑β1 in non‑tumor‑associated CD4+ T cells via the STAT5 signaling pathway. The results of the present study may aid in identifying therapeutics that could further modulate the immune system during BC.Colorectal cancer (CRC) is one of the most common malignant diseases in the world. Although mechanistic studies have been conducted on the pathogenesis of CRC, the molecular mechanism of CRC tumorigenesis remains unclear. In the present study, the weighted gene co‑expression network analysis was performed for the Gene Expression Omnibus (GEO) dataset GSE87211, in order to analyze the key modules involved in the pathogenesis of CRC. Next, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the key module genes to analyze the functional pathways involved. The hub genes were screened using the Cytoscape platform and verified by a second GEO dataset, GSE21510. Finally, 10 hub genes were identified in 2 key modules (the green and brown modules) as the genes most significantly associated with the tumorigenesis of CRC. The 5 hub genes from the green module included collagen type I α1 chain, collagen type XII α1 chain, collagen triple helix repeat containing 1, inhibin subunit βa (INHBA) and chromobox 2 (CBX2), while the 5 hub genes from the brown module included bestrophin 2 (BEST2), carbonic anhydrase 2, glucagon, solute carrier family 4 member 4 and gliomedin. The 2 key modules with the 10 hub genes identified may regulate the occurrence and development of CRC through the extracellular matrix pathway, PI3K‑Akt and chemokine signaling pathways, thus providing a reference for understanding the complex mechanism of tumorigenesis in CRC. Of note, few studies have reported the pathogenesis of CRC with the 3 identified hub genes, INHBA, CBX2 and BEST2. Further investigation of the molecular mechanism of these genes in CRC is recommended.Colorectal cancer (CRC) is a global health concern. The role of epigenetics in tumors has garnered increasing interest. ADP ribosylation is an epigenetic modification that is associated with a variety of biological functions and diseases, and its association with tumor development and progression has been hypothesized. However, due to the limitations of available techniques and methods, ADP ribosylation of specific sites is difficult to determine. In previous studies, it was shown that arginine‑117 of histone 3 (H3R117) in Lovo cells can be modified by mono‑ADP‑ribosylation. This site was mutated and Lovo cells overexpressing this mutant construct were established. In the present study, the expression of differentially expressed genes (DEGs) between untransfected Lovo cells and H3R117A Lovo cells was analyzed. A total of 58,174 DEGs were identified, of which 2,324 were significantly differentially expressed (q‑value 2). Functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment was used to analyze the functions and possible roles of the DEGs. The DEGs were enriched in pathways associated with metabolic process, catalytic activity, organelle and chromatin structure, and dynamics. Through this comprehensive and systematic analysis, the role of mono‑ADP‑ribosylation in CRC was examined, providing a foundation for future studies.The small intestine is one of the most highly regenerative and radiosensitive tissues in mammals, including humans. Exposure to high doses of ionizing radiation causes serious intestinal damage. Recently, several investigations have been conducted using radioprotective agents to determine ways for reducing intestinal damage caused by radiation exposure. However, a thorough understanding of functional changes occurring in the small intestine of mice exposed to high‑dose radiation is necessary for developing novel and more potent radioprotective agents. In this study, we examined changes in microRNA (miRNA/miR) expressions in the small intestine of mice at 72 h after X‑ray exposure (10 Gy). We identified seven upregulated miRNAs and six downregulated miRNAs in the small intestine of mice following radiation exposure using miRNA microarray analysis. Particularly, miR‑34a‑5p was highly expressed, which was confirmed by reverse transcription-quantitative PCR. Forkhead box P1 (Foxp1) was predicted to be a target of the mRNA of miR‑34a‑5p using OmicsNet. Decreased Foxp1 expression in the small intestine following radiation exposure was confirmed, suggesting that Foxp1 expression recovery may induce the suppression of radiation‑induced enteritis. Therefore, miR‑34a‑5p is a potential target molecule for developing novel radioprotective agents.Cutaneous neurofibromas (cNFs) are present in the majority of patients with neurofibromatosis type 1 (NF1), and results in disfigurements of the body, which is associated with psychological distress. A hallmark feature of cNF is the infiltration of inflammatory cells, among which macrophages are an important component of the microenvironment. Loss of neurofibromin (Nf1) expression results in activation of the PI3K and MAPK signaling pathways; however, the therapeutic effects of specific inhibitors targeting these pathways are not satisfactory. The present study showed increased macrophage infiltration accompanied by activation of effectors of the Hippo signaling pathway. Additionally, it was shown that XMU‑MP‑1 enhanced macrophage accumulation, in vivo and in vitro, by elevating the levels of C‑C motif chemokine ligand 5 (CCL5) and transforming growth factor (TGF)‑β1 expression. However, neither CCL5 nor TGF‑β1 ablation alone were able to effectively reverse the XMU‑MP‑1‑induced upregulation of macrophage accumulation, whereas concurrent ablation of these two genes significantly decreased macrophage accumulation. EdU staining and flow cytometry suggested that activated Yes‑associated protein 1 promoted proliferation rather than inhibiting apoptosis in macrophage cells, and this may underlie the increase in the accumulation of macrophages. Both CCL5/C‑C motif chemokine receptor 5 and TGF‑β1/TGFβ1 receptor served crucial roles in modulating macrophage proliferation, which ultimately contributed to macrophage accumulation. The function of the Hippo pathway in the development of cNF development and its potency as a therapeutic target merit further investigation.Celastrol and triptolide, chemical compounds isolated from Tripterygium wilfordii hook (also known as thunder god vine), are effective against rheumatoid arthritis (RA). Celastrol targets numerous signaling pathways involving NF‑κB, endoplasmic reticulum Ca2+‑ATPase, myeloid differentiation factor 2, toll‑like receptor 4, pro‑inflammatory chemokines, DNA damage, cell cycle arrest and apoptosis. Triptolide, inhibits NF‑κB, the receptor activator of NF‑κB (RANK)/RANK ligand/osteoprotegerin signaling pathway, cyclooxygenase‑2, matrix metalloproteases and cytokines. The present review examined the chemistry and bioavailability of celastrol and triptolide, and their molecular targets in treating RA. Clinical studies have demonstrated that T. wilfordii has several promising bioactivities, but its multi‑target toxicity has restricted its application. Thus, dosage control and structural modification of T. wilfordii are required to reduce the toxicity. In this review, future directions for research into these promising natural products are discussed.Ropivacaine, one of the most commonly used local anesthetics in clinical practice, has shown potent antitumor activity in multiple types of cancer cells. However, its effect on cervical cancer cell growth remains unknown. In the present study, it was found that ropivacaine inhibited cervical cancer cell growth by suppressing cell cycle progression and promoting cell apoptosis, as determined by CCK‑8 assay, cell cycle and apoptosis analyses. Western blot analysis and luciferase assay demonstrated that ropivacaine abrogated the phosphorylation and transcriptional activation of signal transducer and activator of transcription 3 (STAT3), and that STAT‑3C overexpression reversed the inhibition of cervical cancer cell viability mediated by ropivacaine. Furthermore, our results revealed that the increased expression of maternally expressed gene 2 (MEG2) caused by ropivacaine led to STAT3 dephosphorylation. Finally, we found that ropivacaine upregulated MEG2 by decreasing the expression of microRNA‑96 (miR‑96). Taken together, our results describe a novel mechanism for the anticancer activity of ropivacaine and suggest ropivacaine as a potential therapeutic agent for cervical cancer patients.The present study aimed to investigate the effects of cold atmospheric plasma (CAP)‑activated Ringer's solution on osteosarcoma cell lines MG63 and U2OS, and to identify the molecular mechanism underlying these effects. CAP‑activated Ringer's solution was used to treat osteosarcoma cell lines MG63 and U2OS for 30 min. Cell viability was measured using the MTT method. The apoptosis rate was detected using Annexin‑V and propidium iodide. The expression levels of cytochrome c, caspase‑3 and polyADP ribose polymerase (PARP) in MG63 cells were analyzed via western blotting. The change in mitochondrial membrane potential was detected via the JC‑1 dye method and verified by the level of reactive oxygen species (ROS). CAP‑activated Ringer's solution inhibited the proliferation of MG63 and U2OS cells in a dose‑ and time‑dependent manner. Furthermore, CAP‑activated Ringer's solution induced the apoptosis of MG63 cells, increased the intracellular ROS level, decreased the mitochondrial membrane potential level, and induced the release of cytochrome c. CAP‑activated Ringer's solution inhibits osteosarcoma cell proliferation through intracellular ROS‑mediated mitochondrial apoptosis.Lung adenocarcinoma is one of the most common malignant tumors worldwide. Although efforts have been made to clarify its pathology, the underlying molecular mechanisms of lung adenocarcinoma are still not clear. The microarray datasets GSE75037, GSE63459 and GSE32863 were downloaded from the Gene Expression Omnibus (GEO) database to identify biomarkers for effective lung adenocarcinoma diagnosis and therapy. The differentially expressed genes (DEGs) were identified by GEO2R, and function enrichment analyses were conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The STRING database and Cytoscape software were used to construct and analyze the protein‑protein interaction network (PPI). We identified 376 DEGs, consisting of 83 upregulated genes and 293 downregulated genes. Functional and pathway enrichment showed that the DEGs were mainly focused on regulation of cell proliferation, the transforming growth factor β receptor signaling pathway, cell adhesion, biological adhesion, and responses to hormone stimulus. Sixteen hub genes were identified and biological process analysis showed that these 16 hub genes were mainly involved in the M phase, cell cycle phases, the mitotic cell cycle, and nuclear division. We further confirmed the two genes with the highest node degree, DNA topoisomerase IIα (TOP2A) and aurora kinase A (AURKA), in lung adenocarcinoma cell lines and human samples. Both these genes were upregulated and associated with larger tumor size. Upregulation of AURKA in particular, was associated with lymphatic metastasis. In summary, identification of the DEGs and hub genes in our research enables us to elaborate the molecular mechanisms underlying the genesis and progression of lung adenocarcinoma and identify potential targets for the diagnosis and treatment of lung adenocarcinoma.We previously reported that relative to normal cervical mucus, microRNA 126‑3p (miR‑126‑3p) is present in significantly greater amounts in the cervical mucus of patients with overt cervical cancer or precursor lesions. Here, we investigated the effects of enforced miR‑126‑3p expression in the cervical cancer cell line, HeLa, on proliferation, migration, invasion, apoptosis and protein expression. We transfected HeLa cells with miR‑126‑3p miRNA and found that proliferation, migration and invasion by cell counting, wound healing, cell migration and invasion assay were significantly reduced in these cells relative to those transfected with a negative control mimic. The levels of phosphoinositide 3 kinase (PI3K), phosphorylated 3‑phosphoinositide‑dependent protein kinase‑1 (p‑PDK1) and p‑AKT proteins were lower in the miR‑126‑3p‑transfected cells. Phosphorylated 70S6K (p‑p70S6K), phosphorylated glycogen synthase kinase 3β (p‑GSK3β), phosphorylated S6K (p‑S6K), cyclin D1, phosphorylated p21‑activated kinase 1 (p‑PAK1), Rho associated coiled‑coil containing protein kinase 1 (ROCK1), myotonic dystrophy‑related CDC42‑binding kinases α (MRCKα) and phospholipase C γ1 (p‑PLCγ1) were also downregulated. This suggests that downstream effectors of the PI3K/PDK1/AKT pathway are targets for inhibition by miR‑126‑3p. In contrast, apoptotic‑related proteins including the BCL‑2‑associated agonist of cell death (Bad), B‑cell lymphoma‑extra‑large (Bcl‑xL) and BCL‑2‑associated X (Bax), were all upregulated by miR‑126‑3p, resulting in increased caspase 3/7 activity and apoptosis. Thus, enforced expression of miR‑126‑3p inhibited cell migration and invasion and also induced apoptosis by regulating the PI3K/PDK1/AKT pathway in HeLa cells. Hence, high levels of miR‑126‑3p may inhibit cervical carcinogenesis, and targeting the PI3K/PDK1/AKT pathway via miR‑126‑3p could represent a new approach for treating patients with cervical cancer.Solanum nigrum L. (Longkui) is one the most widely used anticancer herbs in traditional Chinese medicine. α‑Solanine is an important ingredient of S. nigrum L. and has demonstrated anticancer properties in various types of cancer. However, the effects of α‑solanine on colorectal cancer remain elusive. The aim of the present study was to assess the effects of α‑solanine on human colorectal cancer cells. The results demonstrated that α‑solanine inhibited the proliferation of RKO cells in a dose‑ and time‑dependent manner. In addition, α‑solanine arrested the cell cycle at the G0/G1 phase and suppressed the expression levels of cyclin D1 and cyclin‑dependent kinase 2 in RKO cells. α‑Solanine induced apoptosis of RKO cells, as indicated by morphological changes and positive Annexin‑FITC/propidium iodide staining. Additionally, α‑solanine activated caspase‑3, ‑8 and ‑9 in RKO cells, which contributed to α‑solanine‑induced apoptosis. α‑Solanine also increased the generation of reactive oxygen species, which contributed to caspase activation and induction of apoptosis. α‑Solanine inhibited the migration, invasion and adhesion of RKO cells, as well as the expression levels and activity of matrix metalloproteinase (MMP)‑2 and MMP‑9. In addition, α‑solanine inhibited cell proliferation, activated caspase‑3, ‑8 and ‑9, induced apoptosis, and inhibited the migration and invasion of HCT‑116 cells. Furthermore, α‑solanine inhibited tumor growth and induced apoptosis in vivo. These findings demonstrated that α‑solanine effectively suppressed the growth and metastatic potential of human colorectal cancer.Baicalin is an important flavonoid compound THAT is isolated from the Scutellaria baicalensis Georgi Chinese herb and plays a critical role in anti‑oxidative, anti‑inflammatory, anti‑infection and anti‑tumor functions. Although baicalin can suppress the proliferation of tumor cells, the underlying mechanisms of baicalin in bleomycin (BLM)‑induced pulmonary fibrosis remain to be elucidated. Thus, the aim of the present study was to determine the role of baicalin in pulmonary fibrosis and fibroblast proliferation in rats. Hematoxylin and eosin (H&E) and Masson staining were used to measure the morphology of pulmonary fibrosis, ELIASA kits were used to test the ROS and inflammation, and western blotting and TUNEL were performed to study the apoptosis proteins. In vitro, MTT assay, flow cytometry, western blotting and immunofluorescence were performed to investigate the effects of baicalin on proliferation of fibroblasts. The most significantly fibrotic changes were identified in the lungs of model rats at day 28tration, which was subsequently suppressed by baicalin. Collectively, the results of the present study suggested that baicalin exerted a suppressive effect on BLM‑induced pulmonary fibrosis and fibroblast proliferation.Prostate cancer poses a public health threat to hundreds of people around the world. p62 has been identified as a tumor suppressor, however, the mechanism by which p62 promotes prostate cancer remains poorly understood. The present study aimed to investigate whether p62 promotes proliferation, apoptosis resistance and invasion of prostate cancer cells via the Kelch‑like ECH‑associated protein 1/nuclear factor erytheroid‑derived 2‑like 2/antioxidant response element (Keap1/Nrf2/ARE) axis. Immunohistochemical staining and immunoblotting were performed to determine the protein levels. Rates of proliferation, invasion and apoptosis of prostate cancer cells were assessed using an RTCA system and flow cytometric assays. Levels of reactive oxygen species (ROS) were assessed using Cell ROX Orange reagent and mRNA levels of Nrf2 target genes were detected by qRT‑PCR. It was revealed that p62 increased the levels and activities of Nrf2 by suppressing Keap1‑mediated proteasomal degradation in prostate cancer cells and tissues, and high levels of p62 promoted growth of prostate cancer through the Keap1/Nrf2/ARE system. Silencing of Nrf2 in DU145 cells overexpressing p62 led to decreases in the rate of cell proliferation and invasion and an increase in the rate of cell apoptosis. p62 activated the Nrf2 pathway, promoted the transcription of Nrf2‑mediated target genes and suppressed ROS in prostate cancer. Therefore, p62 promoted the development of prostate cancer by activating the Keap1/Nrf2/ARE pathway and decreasing p62 may provide a new strategy to ameliorate tumor aggressiveness and suppress tumorigenesis to improve clinical outcomes.Glioblastoma (GBM) is the most prevalent and lethal primary intrinsic brain cancer. The disease is essentially incurable, with glioblastomas characterized by resistance to both chemotherapy and radiotherapy, as well as by rapid tumor progression, all of which are mainly ascribed to glioma stem‑like cells (GSLCs). In the present study, an improved model that is more similar to clinical GBM was constructed. Twenty clinical glioma samples were collected to obtain primary low‑grade tumor cells. The cells were either maintained in serum‑free medium as primary glioma‑based cells (PGBCs) or cultured in the same medium with CHIR99021 as GSLCs. Then, the molecular and ultrastructural differences between the two cell groups were determined. Furthermore, the proliferation and migration of the GSLCs were examined and the potential mechanisms were investigated. Finally, temozolomide resistance in vitro and in the mouse model was assessed to study the properties of the induced GSLCs. The primary low‑grade tumor cells extracted from surgical samples were enriched with GSLC properties, with high expression levels of CD133 and Nestin in 100 nM CHIR99021. The GSLCs exhibited high proliferation and migration. Furthermore, the expression of the PI3K/AKT signaling pathway and that of related genes and proteins were significantly enhanced by CHIR99021. The animal study also revealed high levels of STAT3, mTOR, NF‑κB, and VEGF in the GSLC‑transplanted mice. CHIR99021 could stably enhance GSLC properties in patient‑derived glioma samples. It may provide a useful model for further study, helping to understand the pathogenesis of therapeutic resistance and to screen drug candidates.N6‑methyladenosine (m6A) RNA methylation is the most prevalent type of mRNA modification; however, little is known about its function in clear cell renal cell carcinoma (ccRCC). The present study aimed to establish and validate a m6A‑related risk signature as a prognostic factor for patients with ccRCC. Consensus clustering was used to divide patients with ccRCC from The Cancer Genome Atlas (TCGA) cohort (n=489) into three clusters (cluster 1/2/3) based on 19 m6A RNA methylation regulators. In addition, a m6A‑related risk signature was constructed using TCGA data, and its accuracy was validated using data from the International Cancer Genome Consortium (n=91). The prognostic performance of the risk signature was evaluated by Kaplan‑Meier analyses, least absolute shrinkage and selection operator Cox regression, multivariate Cox regression, receiver operating characteristic curves and nomograms. The results revealed that the majority of the 19 m6A RNA methylation regulators were differentially expressed among ctic predictions. These results provided insight into the development of m6A‑targeted treatments for ccRCC.Ki‑67 expression has been widely used in clinical practice as an index to evaluate the proliferative activity of tumor cells. The cutoff for Ki67 expression in order to increase the prognostic value of Ki67 expression in colorectal cancer varies. The present study assessed the relationship between the 25% cutoff for Ki67 expression and prognosis in colorectal cancer in the AJCC‑8 (American Joint Committee on Cancer 8 edition) stratification. The current trial included 1,090 colorectal cancer patients enrolled from 2006 to 2012 at Huzhou Central Hospital. Ki67 expression was classified according to 25% intervals, dividing the patients into four groups. Measurement data were analyzed by ANOVA, and count data by Crosstabs. Bivariate correlation analysis was performed to assess clinicopathological indicators based on Ki67 expression. Disease‑free survival (DFS) and overall survival (OS) based on Ki67 levels were analyzed by the Kaplan‑Meier method. A total of 1,090 patients of the 2,080 enrolled CRC cases were evaluated (52.4%). Invasive depth, tumor differentiation, tumor size, AJCC‑8, positive number of lymph nodes and chemotherapy status showed significant differences in the various Ki67 expression groups (all P0.05). Cox regression analysis showed that invasive depth, lymph node metastasis, tumor differentiation, AJCC‑8 and Ki67 were independent factors affecting colorectal cancer (P=0.030, all others P less then 0.001). In conclusion, a cutoff of 25% for Ki67 expression is a good classification tool. High Ki67 has a close association with poor prognosis in colorectal cancer and independently predicts prognosis in the AJCC‑8 stratification.Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer‑related death among women worldwide. Evidence indicates that posttranscriptional N6‑methyladenosine (m6A) modification modulates BC development. In the present study, we assessed BC and normal tissues to investigate this connection. RNA m6A levels were determined by methylation quantification assay. The effects of methyltransferase‑like 14 (METTL14) gain‑of‑expression or co‑transfection with an m6A inhibitor on cell migration and invasion abilities were determined by Transwell assays. The levels of differentially expressed (DE) miRNAs were verified by real‑time quantitative PCR (RT‑qPCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses (KEGG) were performed to analyze potential function of target genes of the DE miRNAs. The effects of candidate miRNAs modulated by METTL14 on cell migration and invasion abilities were confirmed by Transwell assays. We demonstrated that m6A methyltransferase METTL14 was significantly upregulated in BC tissues compared with normal tissues. METTL14 gain‑ and loss‑of‑expression regulated m6A levels in MCF‑7 and MDA‑MB‑231 cells. The cell function assays revealed that METTL14 overexpression enhanced the migration and invasion capacities of BC cells. Moreover, treatment with the m6A inhibitor suppressed this enhanced cell migration and invasion. Additionally, aberrant expression of METTL14 reshaped the miRNA profile in BC cell lines. The remodeled DE miRNA/mRNA network was found to be most enriched in cancer pathways, and DE miRNAs were enriched in cell adhesion terms. hsa‑miR‑146a‑5p modulated by METTL14 promoted cell migration and invasion. METTL14 modulates m6A modification and hsa‑miR‑146a‑5p expression, thereby affecting the migration and invasion of breast cancer cells.Non‑small cell lung cancer (NSCLC) is the most common type of lung cancer, and numerous oncogenes are associated with this disease. Oxysterol‑binding protein‑related protein 8 (ORP8) is essential for cell growth, migration and the modulation of mitochondrial respiration and morphology. However, the underlying role of ORP8 in NSCLC remains unclear. In the present study, it was reported that the expression of ORP8 was low in NSCLC cells and tissues. The ORP8 expression levels were analyzed by immunohistochemistry (IHC), quantitative real‑time PCR (qPCR) and western blot analysis. ORP8 overexpression inhibited cell growth and induced apoptosis in NSCLC cells with MTS, anchorage‑independent growth and Hoechst 33342 staining assay. Further experiments demonstrated that ORP8 overexpression induced the apoptosis of NSCLC cells via the release of cytochrome c from mitochondria into the cytoplasm with western blot analysis and confocal microscopy results. In addition, qPCR analysis showed that miR‑421 was upregulated in NSCLC cell lines, with the bioinformatics analysis, western blot analysis and Dual‑Luciferase reporter assay, it was determined that miR‑421 could target ORP8. The inhibition of cell proliferation via ORP8 overexpression was rescued by a miR‑421 mimic, which aided in maintaining the proliferative potential of the cells. Overall, the present study revealed that ORP8 may be a candidate target in the prevention and treatment of NSCLC.Radiotherapy (RT) has been used as a therapeutic option for treatment of prostate cancer (PCa) for a number of years; however, patients frequently develop RT resistance, particularly in castration‑resistant PCa (CRPC), although the underlying mechanisms remain unknown. Understanding the underlying mechanism of RT resistance in CRPC may potentially highlight novel targets to improve therapeutic options for patients with PCa. In the present study, the expression levels of phospholipase Cε (PLCε), androgen receptor (AR) and DNA‑dependent protein kinase catalytic subunit (PKcs) were examined in PCa tissue samples and PCa cells, and the effects of PLCε knockdown on AR and DNA damage repair (DDR)‑related molecules were determined. The association between PLCε, AR and Poly (ADP‑ribose) polymerase 1 (PARP1), as well as their respective roles in radiation resistance, were assessed using gene knockdown and pharmaceutical inhibitors or activators. A chromatin immunoprecipitation assay was used to determine the epigenetic regulatory effects of PLCε on PARP1. Animal experiments were performed to assess whether the mechanisms observed in vitro could be replicated in vivo. The expression levels of PLCε, AR and DNA‑PKcs were significantly upregulated in PCa, particularly in CRPC. PLCε knockdown reduced the viability and increased apoptosis of cells subjected to radiation. Additionally, PLCε deficiency suppressed DDR progression by downregulating an AR and PARP1 positive feedback loop and the associated downstream molecules following radiation. PLCε depletion also increased the presence of histone H3 lysine 27 trimethylation in the PARP1 promoter region, suggesting increased methylation of the PARP1 gene and thus resulting in reduced expression of PARP1. In vivo, PLCε knockdown significantly potentiated the effects of radiation on tumor growth. Taken together, the results of the present study demonstrated that PLCε knockdown enhanced the radiosensitivity of CRPC by downregulating the AR/PARP1/DNA‑PKcs axis.Accumulating evidence suggests that lncRNAs are involved in almost all normal physiological processes and that aberrant expression of lncRNAs may be involved in the development of diseases, including non‑small cell lung cancer (NSCLC). However, the roles of lncRNA‑TPTE pseudogene 1 (TPTEP1) in lung cancer and the underlying molecular mechanisms have remained elusive. In the present study, significant downregulation of TPTEP1 in tumors compared with normal tissues from patients with NSCLC was observed. Overexpression of TPTEP1 inhibited cell proliferation and induced apoptosis in NSCLC cells. A bioinformatics analysis based on miRDB predicted microRNA (miR)‑328‑5p as a potential binding miRNA for TPTEP1. Using a dual‑luciferase reporter assay and western blot analysis, it was further validated that TPTEP1 sponged miR‑328‑5p to upregulate Src kinase signaling inhibitor 1 (SRCIN1) in NSCLC cells. Through regulation of SRCIN1, TPTEP1 was indicated to inactivate the Src and STAT3 pathways in NSCLC cells. Notably, silencing of SRCIN1 reversed the TPTEP1 overexpression‑induced inhibition of cell proliferation and increase of the apoptotic rate in NSCLC cells. Pearson correlation analysis revealed a significant positive correlation between TPTEP1 and SRCIN1 mRNA levels in NSCLC tumors. The present results provided insight into the roles of TPTEP1 in NSCLC and the underlying mechanisms.Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family and is expressed in a plethora of cancers. The biological roles of AREG in the regulation of the epithelial‑mesenchymal transition (EMT) in pancreatic cancer remain unclear. To investigate the expression of epidermal growth factor receptor (EGFR) and AREG in pancreatic cancer cell lines, RT‑qPCR, western blot analysis, and ELISA were performed. RNAi and exogenous AREG treatment were used to alter AREG expression. Wound‑healing and Transwell assays were performed to evaluate cell migration and invasion abilities. Western blot analysis and immunofluorescence staining were utilized to detect the expression of EMT markers. The protein expression of potential key factors involved in EMT, as well as those of the ERK, AKT, STAT3 and NF‑κB pathways, were analysed by western blotting. The role of AREG in tumour growth in vivo was further determined using an orthotopic model of pancreatic cancer. Knockdown of AREG inhibited AsPC‑1 cell migration and invasion. AREG knockdown upregulated E‑cadherin but downregulated vimentin, Snail and Slug expression in AsPC‑1 cells. In addition, AREG stimulation increased cell migration, invasion and EMT in PANC‑1 cells, and an NF‑κB inhibitor decreased AREG‑induced cell migration, invasion and EMT in PANC‑1 cells. AREG stimulation increased the nuclear accumulation of NF‑κB through the EGFR/ERK signalling pathway to induce EMT. Tumour growth and metastasis were decreased by AREG silencing in an orthotopic model of pancreatic cancer. AREG may play a critical role in cell migration, invasion, and EMT by activating the EGFR/ERK/NF‑κB signalling pathway in pancreatic cancer cells.Ovarian cancer is the most lethal gynecological cancer worldwide. To date, the therapeutic approaches available for the treatment of ovarian cancer are still very limited. The present study first demonstrated that the Chinese herb, Oroxylin A, exerts inhibitory effects on both the migratory ability and viability of ovarian cancer cells. Notably, the inhibitory effects of the drug occurred in a dose‑dependent manner. Oroxylin A only inhibited cell migration at the lower dose, whereas it induced early or late apoptosis at the middle or higher doses, respectively. Mechanistically, Oroxylin A increased peroxisome proliferator‑activated receptor gamma (PPARγ) expression and altered the expression profile of progesterone receptor membrane component (PGRMC)1/2. Notably, PPARγ was revealed to play a central role in Oroxylin A‑mediated anticancer activity. The silencing of PPARγ significantly abrogated Oroxylin A‑induced apoptotic cell death and restored the expression profile of the PGRMC1/2 family in ovarian cancer cells. Collectively, the present study revealed that Oroxylin A exerted marked anticancer effects against ovarian cancer in vitro. Thus, Oroxylin A may have potential for use as a complementary therapy in the treatment of ovarian cancer.
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