title: The HIF-2α-MALAT1-miR-216b axis regulates multi-drug resistance of hepatocellular carcinoma cells via modulating autophagy.
abstract: In this study, we firstly investigated the association among lncRNA MALAT1, HIF-1α and HIF-2α in hepatocellular carcinoma (HCC) cells. Then, we investigated the regulative effect of MALAT1 on multi-drug resistance (MDR) in HCC cells and the underlying mechanism. The results showed that MALAT1 was over two times higher in BEL-7402/5-FU cells than in BEL-7402 cells. It was HIF-2α, but not HIF-1α induced MALAT1 upregulation in HCC cells. Dual luciferase assay demonstrated that there were at least two binding sites of miR-26b in MALAT1. Therefore, we infer that there is a HIF-2α-MALAT1-miR-216b axis in HCC cells. Cell viability assay showed that both MALAT1 siRNA and miR-216b mimics reduced IC50 of 5-FU, ADR and MMC in BEL-7402/5-FU cells. MALAT1 siRNA and miR-216b mimics showed similar effect as 3-MA on reducing LC3-II levels, inhibiting p62 degradation and suppressing GFP-LC3 puncta formation in BEL-7402/5-FU cells. Flow cytometric analysis showed that 3-MA treatment, MALAT1 siRNA and miR-216b mimics all promoted 5-FU induced apoptosis in BEL-7402/5-FU cells. Therefore, this study firstly revealed that there is a HIF-2α-MALAT1-miR-216b axis regulating MDR of HCC cells via modulating autophagy.
authors.affiliation: Department of Interventional Therapy, The People's Hospital of Jianhu, Jianhu, 224700, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Department of Hematology & Oncology, Yeda Hospital, Yantai, 264006, Shandong, China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Emergency Medicine, The Affiliated Hospital of WeiFang Medical University, WeiFang, 261031, Shandong, China.
authors.forename: Quanling
authors.initials: Q
authors.lastname: Zang
authors.affiliation: Department of Oncology, The Affiliated Hospital of WeiFang Medical University, WeiFang, 261031, Shandong, China.
authors.forename: Guixin
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Infectious Liver Diseases, Zaozhuang Municipal Hospital, Zaozhuang, 277100, Shandong, China.
authors.forename: Xiangfei
authors.initials: X
authors.lastname: Guo
authors.affiliation: Oncology Department, The Affiliated Hospital of Hebei University of Engineering, Handan, 056029, Hebei, China. Electronic address: Jianghef@outlook.com.
authors.forename: Jianghe
authors.initials: J
authors.lastname: Fan
mesh_terms: D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004317:Doxorubicin; D005472:Fluorouracil; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D000099162:Endothelial PAS Domain-Containing Protein 1; C557041:MALAT1 long non-coding RNA, human; C575482:MIRN216 microRNA, human
keywords: Autophagy; HCC; HIF-2α; MALAT1; Multi-drug resistance; miR-216b