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Given that tNOX catalyzes the oxidation of NADH, the direct binding of capsaicin to tNOX also inhibited the NAD+-dependent activity of sirtuin 1 (SIRT1) deacetylase, we found that capsaicin-induced autophagy involved enhanced acetylation of ULK1, which is a key player in autophagy activation, possibly through SIRT1 inhibition. In p53-mutated HSC-3 cells, capsaicin triggered both autophagy and apoptosis. In this case, autophagy occurred before apoptosis during this early stage, autophagy seemed to inhibit apoptosis; at a later stage, in contrast, autophagy appeared to be essential for the induction of apoptosis. Western blot analysis revealed that the reduction in tNOX and SIRT1 associated with enhanced ULK1 acetylation and c-Myc acetylation, which in turn, reactivated the TRAIL pathway, ultimately leading to apoptosis. Taken together, our data highlight the potential value of leveraging capsaicin and tNOX in therapeutic strategies against oral cancer.The precise molecular mechanism of hepatocellular carcinoma (HCC) remains ambiguous. Isocitrate dehydrogenase 3A (IDH3A) is known as a subunit of the IDH3 heterotetramer. To the best of our knowledge, the biological effect of IDH3A in malignant tumors is unclear. Here, we report that IDH3A is significantly upregulated in HCC tissues; moreover, high expression of IDH3A is strongly associated with tumor size and the clinicopathologic stage of HCC. RNA-seq revealed that depletion of IDH3A affects the expression of metastasis associated 1 (MTA1), an oncogene which is related to the progression of numerous cancer types to the metastasis stage. Cell transfection was used to upregulate and downregulate the expression of IDH3A in HCC cells. The migration activity of HCC cells was assessed using wound healing assays. While transwell assays were carried out to detect the invasion of HCC cells. RNA-seq, RT-qPCR and western blot were used to validate MTA1 as a potential target gene. The present study suggested that IDH3A can upregulate MTA1 expression and promote epithelial-mesenchymal transition (EMT) in HCC by inducing MTA1 expression, thereby facilitating cell migration and invasion of HCC cells. Here, we demonstrated the importance of IDH3A in HCC progression. The identification of the IDH3A axis provides novel insight into the pathogenesis of HCC, and the IDH3A axis might represent a novel target for the treatment of HCC.Cytochrome P450 3A5 (CYP3A5) maintains primary roles in toxic metabolism, catalyzes redox reaction, and contributes to chemotherapeutic resistance. However, the mechanism of CYP3A5 in carcinogenesis remains largely undefined. Here, we investigated a novel role of CYP3A5 inhibiting the metastasis in lung adenocarcinoma (LUAD) via ATOH8/Smad1 axis. We found that CYP3A5 was generally down-regulated in LUAD by RT-PCR, western blot and immunohistochmeistry (IHC) in tissues and cell lines. Low expression of CYP3A5 was significantly associated with poor prognosis of LUAD patients. Functionally, ectopic expression of CYP3A5 could substantially inhibit the migration and invasion in vitro. Consistently, up-regulation of CYP3A5 dramatically suppressed metastatic ability in vivo. Mechanistically, high-throughput phosphorylation chip indicated that CYP3A5 significantly decreased the phosphorylation of Smad1, resulting in suppression of metastasis. Estrogen chemical Furthermore, bioinformatics analysis and co-immunoprecipitation (Co-IP) experiments uncovered that CYP3A5 interacted with ATOH8, and the interaction, in turn, mediated in-activation in the Smad1 pathway. The combined IHC panel, including CYP3A5 and phosphorylation of Smad1, exhibited a better prognostic value for LUAD patients than any of these components individually. Taken together, CYP3A5 repressed activation of Smad1 to inhibit LUAD metastasis via interacting with ATOH8, indicating a novel potential mechanism of CYP3A5 in LUAD progression.Ovarian cancer is a gynecological malignant tumor with a high morbidity. Livin is a novel member of the inhibitor of apoptosis protein family, which is expressed in various malignant tumors and is suggested to be a poor prognostic factor. However, the prognostic significance of Livin and the molecular mechanisms by which Livin promotes ovarian cancer progression are poorly understood. In this study, the upregulation of Livin was confirmed both in primary specimens from ovarian cancer patients and in ovarian cancer cell lines compared to normal controls in vitro. Overexpression of specific Livin transcripts promoted cell growth and migration in vitro, while knockdown of Livin expression suppressed these cellular processes. These effects of the Livin gene were also demonstrated in a xenograft mouse model. Mechanistic studies further revealed that Livin promotes the proliferation and invasion of ovarian cancer cells by activating the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway. Furthermore, we revealed that inhibition of YAP by short-hairpin RNA prevents the growth and invasion of ovarian cancer cells in vivo and in vitro. Therefore, Livin may be a potential novel therapeutic target for the treatment of ovarian cancer.Hepatocellular carcinoma (HCC) patients always have a background of cirrhosis. Aberrant epigenetic changes in cirrhosis provide a conductive environment for HCC tumorigenesis. Active enhancers (AEs) are essential for epigenetic regulation and play an important role in cell development and the progression of many diseases. However, the role of AEs in the progression from cirrhosis to HCC remains unclear. We systemically constructed a landscape of AEs that developed de novo in cirrhosis and were conserved in HCC, referred to as CL-HCC AEs. We observed significant upregulation of these CL-HCC AE-associated genes in cirrhosis and HCC, with no other epigenetic changes. Enrichment analysis of these CL-HCC AE-associated genes revealed enrichment in both hepatocyte-intrinsic tumorigenesis and tumor immune response, which might contribute to HCC tumorigenesis. Analysis of the diagnostic ability of these CL-HCC AE-associated genes provided a five-gene (THBS4, OLFML2B, CDKN3, GABRE, and HDAC11) diagnostic biomarker for HCC.
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