title: MicroRNA-30a sensitizes tumor cells to cis-platinum via suppressing beclin 1-mediated autophagy.
abstract: Autophagy is activated in cancer cells during chemotherapy and often contributes to tumor chemotherapy resistance. In this study, we characterized the role of microRNA-30a (miR-30a) in the coordination of cancer cell apoptosis and autophagy, which determines the sensitivity of cancer cells to chemotherapy. First, the autophagy activity in cancer cells increased after cis-dichloro-diamine platinum (cis-DDP) or Taxol treatment, as indicated by the enhanced expression of beclin 1, a key regulator of autophagy, and increased number of LC3-positive autophagosomes. Second, miRNA screening using a TaqMan probe-based quantitative RT-PCR assay identified that miR-30a, a miRNA that targets beclin 1, was significantly reduced in tumor cells by cis-DDP treatment. Forced expression of miR-30a significantly reduced beclin 1 and the autophagy activity of tumor cells induced by cis-DDP. Third, the blockade of tumor cell autophagy activity by miR-30a expression or 3-methyladenine significantly increased tumor cell apoptosis induced by cis-DDP treatment. Finally, an in vivo tumor implantation mouse model clearly showed that elevation of miR-30a in implanted tumor cells by administration of the recombinant lentivirus expressing miR-30a strongly enhanced cis-DDP-induced apoptosis of tumor cells. In conclusion, our results demonstrate for the first time that miR-30a can sensitize tumor cells to cis-DDP via reducing beclin 1-mediated autophagy and that increasing miR-30a level in tumor cells represents a novel approach to enhance the efficacy of chemotherapy during cancer treatment.
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Zhenyou
authors.initials: Z
authors.lastname: Zou
authors.forename: Linping
authors.initials: L
authors.lastname: Wu
authors.forename: Hanying
authors.initials: H
authors.lastname: Ding
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D016086:Lentivirus; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C546086:MIRN30b microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D002945:Cisplatin