title: miR-101 inhibits autophagy and enhances cisplatin-induced apoptosis in hepatocellular carcinoma cells.
abstract: Hepatocellular carcinoma (HCC) ranks third in cancer-related mortality due to late diagnosis and poor treatment options. Autophagy is a lysosome-mediated protein and organelle degradation process which is characterized by the formation of double-membrane vesicles, known as autophagosomes. Increasing evidence reveals that autophagy functions as a survival mechanism in liver cancer cells against drug-induced apoptosis. In this study, we found that autophagy was suppressed by miR-101 in the HCC cell line HepG2. miR-101 inhibited autophagy via targets including RAB5A, STMN1 and ATG4D. Moreover, miR-101 enhanced apoptosis induced by cisplatin in the HepG2 cell line. The possible mechanism of this effect may be through inhibition of autophagy. Our results indicate a novel and critical role for miR-101 and autophagy in the chemoresistance of cisplatin in HCC. We propose that gene therapy targeting miR-101/autophagy should be investigated further as a potential alternative therapeutic strategy for HCC.
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu 210029, PR China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: An
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Changhe
authors.initials: C
authors.lastname: Zhang
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.forename: Changjun
authors.initials: C
authors.lastname: Huang
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D050777:Stathmin / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000071183:Autophagy-Related Proteins; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; C493995:STMN1 protein, human; D050777:Stathmin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C543490:ATG4D protein, human; D003546:Cysteine Endopeptidases; D020696:rab5 GTP-Binding Proteins; D002945:Cisplatin