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New Kind of Preclinical Studies: Variety of PDX Lines as opposed to Subsampling within just PDX Outlines.
Importantly, upregulation of FOXA2 restored the carcinogenesis of miR-1246 in melanoma. Conclusion MiR-1246 promoted cell viability and metastasis in melanoma by inhibiting FOXA2 expression. © 2020 Yu et al.Aim Cullin 4B (CUL4B) is a member of the cullin ubiquitin-ligase family, which participates in proteolysis. Aberrant CUL4B expression has been shown in many malignancies. This study aimed to elucidate oncogenic role of CUL4B in gastric cancer (GC). https://www.selleckchem.com/products/dl-alanine.html Methods CUL4B expression in GC tissues was examined by RT-PCR and immunohistochemistry. The proliferation, invasion and tumorigenicity of GC cells with CUL4B overexpression or knockdown were evaluated. Results CUL4B expression significantly increased in GC tissues, and was correlated to UICC stage and differentiation of GC, as well as poor overall survival and disease-free survival. Both univariate and multivariate analysis identified CUL4B as an independent predictor for GC patient prognosis. In addition, CUL4B promoted GC cell proliferation and invasion in vitro and tumor formation in vivo. Conclusion CUL4B is overexpressed to promote GC development and progression. CUL4B is a promising prognostic marker and therapeutic target for GC. © 2020 Wu et al.Background Our previous study demonstrated that Id-1 may promote the tumorigenicity of esophageal squamous cell carcinoma (ESCC). Id-4 is another member of Id family, which is rare to be studied in ESCC. In this study, we investigated the expression of Id-4 in human ESCC specimens and determined whether Id-4 expression was associated with the clinicopathologic characteristic and the prognosis of ESCC patients. Methods We examined Id-4 expression using immunohistochemistry in 92 ESCC tissues and adjacent normal tissues. The association between Id-4 expression and clinical parameters and survival was evaluated by statistical analysis. Cox regression analyses were conducted to identify prognostic factors associated with overall survival (OS). In addition, we explored the functional mechanism of Id-4 in ESCC. Results Id-4 expression was significantly downregulated in ESCC tissues compared with adjacent normal tissues. The expression of Id-4 was associated negatively with pT stage (p=0.002), AJCC stage (p=0.008) athway. Thus, we believe that Id-4 may be a promising prognostic marker and a therapeutic target in ESCC. © 2020 Wang et al.Background 6-thioguanine (6-TG), as a conventional "ancient" drug for the treatment of acute leukemia, has been proved to have extensive anti-tumor roles. This study was created to investigate the hidden function of 6-TG on the MCF-7 breast cancer cell line (ER+, PR+) and its mechanisms. Methods MCF-7 cells were treated with 6-TG, and the IC50 value was measured by a cell counting kit-8 assay. Differentially expressed genes (DEGs) were confirmed by RNA-seq analysis. Apoptosis and cell cycle consequences were determined by flow cytometry and Western blot analyses. Results The results showed that colony formation decreased markedly and the percentage of cell apoptosis increased after 6-TG treatment. DNMT1 mRNA and protein expression decreased, and FAS expression increased. Moreover, 6-TG also induced MCF-7 cells to undergo G2/M phase cell cycle arrest and upregulated CDKN1A (p21). Conclusion Overall, our results suggest that 6-TG may induce FAS-mediated exogenous apoptosis and p21-dependent G2/M arrest by inhibiting the activity of DNMT1 in MCF-7 breast cancer cells. © 2020 Li et al.Purpose Colorectal cancer (CRC) is the third most common cancer, and the second leading cause of cancer death worldwide. Dysregulation of microRNAs has been shown to modulate glucose metabolic reprogramming in CRC. However, the functional role of miR-4999-5p in the CRC glucose metabolic shift has not been characterized. Patients and Methods The levels of miR-4999-5p and PRKAA2 were evaluated by RT-qPCR. Univariate and multivariate survival analyses were conducted to evaluate the prognostic value of miR-4999-5p. Cell proliferation was assessed using the CCK-8 and colony formation assays. Extracellular acidification rate, glucose uptake, cellular glucose-6-phosphate level, and lactate production were evaluated to assess the effects of miR-4999-5p on CRC glycolysis. Dual-luciferase reporter assay was conducted to investigate the direct interaction between miR-4999-5p and PRKAA2. Mouse xenograft models were established to assess the functions of miR-4999-5p in vivo. Results miR-4999-5p was highly expressed in CRC tissues and cell lines. In addition, miR-4999-5p was associated with tumor differentiation and TNM stage, and elevated expression of miR-4999-5p was an independent predictor of poorer overall survival. Furthermore, miR-4999-5p promoted cell proliferation and glycolysis in CRC. miR-4999-5p targeted PRKAA2 to exert its tumor-promoting functions, and PRKAA2 knockdown rescued decreased cell proliferation and glycolysis in miR-4999-5p-silenced CRC cells. In vivo experiments showed that miR-4999-5p promoted CRC growth. Conclusion miR-4999-5p facilitated cell growth and glucose metabolic reprogramming through direct targeting of PRKAA2. Our results showed that miR-4999-5p may be a novel prognostic marker and therapeutic target for CRC. © 2020 Zhang et al.Purpose To explore the regulatory effect of HMGB1 upon hypoxia-induced mitochondrial biogenesis in pancreatic cancer PANC1/CFPAC1 cells. Methods After a down-regulation of HMGB1 expression by lentivirus-mediated RNAi, the effect of knocking down HMGB1 on hypoxia-induced mitochondrial biogenesis was examined. NRF-1/TFAM expression, mtDNA copy number, ATP content and mitochondrial number/morphology in hypoxia-treated pancreatic cancer cells were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, mtDNA and ATP assay kits and electron microscopy, respectively. Cell proliferation was measured by MTS assay. And protein and acetylation levels of PGC-1α and SIRT1 activity were detected by Western blot, immunoprecipitation (IP) and SIRT1 activity kit. Results Hypoxia enhanced the expressions of NRF-1/TFAM, boosted mtDNA copy number and ATP content and increased the number of mitochondria in pancreatic cancer cells while induction was suppressed by a knockdown of HMGB1. Knocking down HMGB1 expression lowered hypoxia-induced PGC-1α/SIRT1 expression and activity, phosphorylation of AMPK.
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