MiR-23a-mediated inhibition of topoisomerase 1 expression potentiates cell response to etoposide in human hepatocellular carcinoma

• Published in: Molecular cancer 2013-10, Vol.12 (1), p.119-119, Article 119
• Main Authors: Wang, Ning, Zhu, Meifen, Tsao, Sai-Wah, Man, Kwan, Zhang, Zhangjin, Feng, Yibin
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; 5-Fluorouracil; Analysis; Animals; Antigens, Neoplasm - metabolism; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Base Sequence; Binding Sites; Cancer; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Care and treatment; Cell Line, Tumor; Chemotherapy; Cytotoxicity; Diagnosis; DNA Topoisomerases, Type I - genetics; DNA Topoisomerases, Type I - metabolism; DNA Topoisomerases, Type II - metabolism; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - metabolism; Drug Resistance, Neoplasm; Etoposide; Etoposide - pharmacology; Experiments; Fluorouracil; Fluorouracil - pharmacology; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Hepatoma; Humans; Liver cancer; Liver Neoplasms, Experimental - drug therapy; Liver Neoplasms, Experimental - metabolism; Liver Neoplasms, Experimental - pathology; Medicine; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNA; MicroRNAs - genetics; Poly-ADP-Ribose Binding Proteins; Regulation; RNA Interference; Studies; Tumor Burden; Tumor proteins; Tumor Suppressor Protein p53 - metabolism; Xenograft Model Antitumor Assays
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/1476-4598-12-119

microRNAs have been shown to regulate the chemosensitivity of cancer cells. The aim of this study is to investigate the role and mechanism of mir-23a in enhancing the anti-tumor effect of topoisomerase 2A (TOP2A) poison etoposide in human hepatocellular carcinoma (HCC). The anti-tumor effect of chemotherapeutic agents in HCC cells were examined in vitro and in vivo xenograft model. Expression of mRNA and miRNAs were determined by quantitative real-time PCR. Protein expression was analyzed by immunoblotting. Overexpression of mir-23a could significantly potentiate the in vitro and in vivo anti-tumor effect of etoposide; however, ectopic expression of miR-23a fails to sensitize HCC cells to 5-fluorouracil treatment, indicating the miR-23a-induced cancer cell hypersensitivity in chemotherapy is TOP2A-specific though miR-23a overexpression could not directly up-regulate TOP2A expression. Topoisomerase 1(TOP1) is down-regulated in miR-23a-overexpressed HCC cells. MiR-23a could directly bind to 3'untranslated region of TOP1 mRNA, and suppress the corresponding protein expression and inhibition of miR-23a further arguments the expression of TOP1. MiR-23a was up-regulated during DNA damage in cancer cells in line with the p53 expression. Up-regulation of p53 induces mir-23a expression, while suppression of p53 inhibits miR-23a in HCC cells. Our study sheds light on the role of miR-23a as a potential target in regulating chemosensitivity of HCC cells.