title: Up-regulation of miR-877 induced by paclitaxel inhibits hepatocellular carcinoma cell proliferation though targeting FOXM1.
abstract: Paclitaxel is an effective chemotherapeutic agent for treatment of cancer patients, and frequently, clinical outcome is influenced by paclitaxel sensitivity. Despite this, our understanding of the molecular basis of paclitaxel response is incomplete. Recently, it has been shown that microRNAs (miRNAs) influence messenger RNA (mRNA) transcriptional control and can contribute to human carcinogenesis. In the present study, our objective was to identify miR-877 associated with HCC cell lines response to paclitaxel and to evaluate these miRNAs as therapeutic targets to increase paclitaxel sensitivity. We measured the expression of miR-877 in paclitaxel-treated HCC cell lines. We verified that miR-877 was up-regulated in paclitaxel-induced HCC cells by real-time PCR. We further investigated the role and mechanisms of miR-877. Over-expression of miR-877 in HCC cells partially restores paclitaxel sensitivity. The proliferation activity and the colony formation activity of HCC cells were both inhibited after transfected with miR-877. MiRNA targets prediction algorithms imply FOXM1 serves as a target gene for miR-877. A fluorescent reporter assay confirmed that miR-877 binds specifically to the predicted site of the FOXM1 mRNA 3'-untranslated region (3'UTR). When miR-877 was overexpressed in HCC cells, the protein levels of FOXM1 was downregulated. These results indicate that miR-877 could influence the sensitivity of paclitaxel treatment in hepatocellular carcinoma cell lines by targeting FOXM1.
authors.affiliation: Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health Nanjing 210029, China.
authors.forename: Xinli
authors.initials: X
authors.lastname: Huang
authors.affiliation: Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health Nanjing 210029, China.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Qin
authors.affiliation: Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health Nanjing 210029, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D017239:Paclitaxel / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C570298:MIRN877 microRNA, human; D035683:MicroRNAs; D017239:Paclitaxel
keywords: FOXM1; Hepatocellular carcinoma; miR-877; paclitaxel