Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Because of the relatively chemotherapy-refractory nature of HCC and significant potential poor hepatic reserve, chemotherapy has not been used consistently in the treatment of HCC. Effective new drugs for HCC are urgently needed. Teriflunomide, which was approved for the treatment of relapsing forms of multiple sclerosis (MS), has been identified as a potential antineoplastic drug. Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts longer than 200 nucleotides that lack protein coding potential. In this study, we investigated the ability of teriflunomide to act as an antineoplastic drug by examining the effects of teriflunomide treatment on HCC cells. Teriflunomide strongly inhibited the proliferation of HCC cells, induced cell apoptosis and induced cell accumulation in S phases of the cell cycle. LncRNA and mRNA expression profiles of HCC cells treated with teriflunomide compared with controls were performed by using microarray analysis. For comparison, the differentially expressed mRNAs were annotated by using gene ontology (GO) and pathway analyses. The microarray revealed that 2085 lncRNAs and 1561 mRNAs differed in the cells treated with teriflunomide compared with controls. Several GO terms including protein folding, mitochondrial outer membrane, transmembrane receptor protein phosphatase activity, negative regulation of cellular biosynthetic process, DNA packaging complex, and receptor signaling protein activity were enriched in gene lists, suggesting a potential correlation with the action mechanism of teriflunomide. Pathway analysis then demonstrated that JAK-STAT signaling pathway may play important roles in the cell apoptosis induced by teriflunomide. Co-expression network analysis indicated that a number of lncRNAs and mRNAs were included in the co-expression network, and p34710_v4 is the lncRNA with highest degree. Then the mRNAs associated with those differentially expressed lncRNAs were also annotated by using gene ontology (GO) and pathway analyses. The pathway analyses shows that teriflunomide significantly inhibited cell proliferation and promoted cell apoptosis partly by participating in Wnt signaling pathways. These findings suggest that teriflunomide could be a potential drug for chemotherapy and molecularly targeted therapies of HCC.
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PMID:Long non-coding RNAs as targets for immunosuppressive drug teriflunomide in anti-cancer potential for hepatocellular carcinoma. 3303 97

Hepatitis B x protein (HBx) affects cellular protein expression and participates in the tumorigenesis and progression of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Metabolic reprogramming contributed to the HCC development, but its role in HBV-related HCC remains largely unclear. Tyrosine-protein phosphatase nonreceptor type 13 (PTPN13) is a significant regulator in tumor development, however, its specific role in hepatocarcinogenesis remains to be explored. Here, we found that decreased PTPN13 expression was associated with HBV/HBx. Patients with low PTPN13 expression showed a poor prognosis. Functional assays revealed that PTPN13 inhibited proliferation and tumorigenesis in vitro and in vivo. Further mechanistic studies indicated that HBx inhibited PTPN13 expression by upregulating the expression of DNMT3A and interacting with DNMT3A. Furthermore, we found that DNMT3A bound to the PTPN13 promoter (-343 to -313 bp) in an epigenetically controlled manner associated with elevated DNA methylation and then inhibited PTPN13 transcription. In addition, we identified IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. We verified the significant negative correlations between PTPN13 expression and c-Myc, PSPH, and SLC7A1 expression in clinical HCC tissue samples. In summary, our findings demonstrate that PTPN13 is a novel regulator of HBV-related hepatocarcinogenesis and may play an important role in HCC. PTPN13 may serve as a prognostic marker and therapeutic target in HBV-related HCC patients.
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PMID:Anti-oncogene PTPN13 inactivation by hepatitis B virus X protein counteracts IGF2BP1 to promote hepatocellular carcinoma progression. 3305 95


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