LncRNA H19 modulated by miR-146b-3p/miR-1539-mediated allelic regulation in transarterial chemoembolization of hepatocellular carcinoma
| Autor: | Liqing Zhou, Nasha Zhang, Ming Yang, Huaixin Xing, Yemei Song |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Carcinoma Hepatocellular Genotype Health Toxicology and Mutagenesis Antineoplastic Agents Single-nucleotide polymorphism Toxicology Polymorphism Single Nucleotide Cell Line Tumor microRNA Humans Medicine SNP Chemoembolization Therapeutic Allele Alleles Aged Aged 80 and over business.industry Proportional hazards model Liver Neoplasms Hep G2 Cells General Medicine Middle Aged Prognosis medicine.disease digestive system diseases female genital diseases and pregnancy complications Oxaliplatin MicroRNAs Gene Knockdown Techniques Hepatocellular carcinoma embryonic structures Cancer research Female RNA Long Noncoding business Genome-Wide Association Study medicine.drug |
| Zdroj: | Archives of Toxicology. 95:3063-3070 |
| ISSN: | 1432-0738 0340-5761 |
| Popis: | Transarterial chemoembolization (TACE) is an effective treatment for unresectable hepatocellular carcinoma (HCC) patients. Although overall survival (OS) of TACE-treated patients has been evidently prolonged, not all unresectable HCC patients can benefit from TACE. Genome-wide association studies identified multiple HCC susceptibility single nucleotide polymorphisms (SNPs). However, it is still unclear how lncRNAs and their functional SNPs impact therapeutic responses of TACE. In the study, we hypothesized that the functional lncRNA H19 SNP(s) might impact H19 expression and, thus, prognosis of TACE-treated HCC patients. We found that the H19 rs3741219 SNP was significantly associated with OS of HCC patients received TACE. Cox proportional hazards model demonstrated that the rs3741219 CC genotype was associated with longer OS and a 37% decreased death risk compared with the TT carriers after TACE therapy (P = 0.001). Interestingly, the rs3741219 T-to-C change led to allelic down-regulation of lncRNA H19 expression via creating the binding sites of miR-146b-3p and miR-1539. Luciferase reporter gene assays indicated that miR-146b-3p and miR-1539 could markedly silence the rs3741219 C-allelic H19 expression but not lncRNA H19 with the T allele. Consistently, there was significantly reduced expression of lncRNA H19 in HCC and normal tissues of the C allele carriers compared with the H19 levels in patients with the T allele. Knock-down of lncRNA H19 significantly promoted the anti-viability efficiency of oxaliplatin (the main chemotherapy drug used in TACE) to HCC cells. In view of these results, we assume that lncRNA H19 might be a potential therapeutic target for unresectable HCC patients. |
| Databáze: | OpenAIRE |
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