title: MicroRNA-98 sensitizes cisplatin-resistant human lung adenocarcinoma cells by up-regulation of HMGA2.
abstract: This study was done to explore the role of microRNA-98 (miR-98) in cisplatin sensitization in human lung adenocarcinoma cell line. Differential expressions of miRNAs were analysed between cisplatin-resistant human lung adenocarcinoma cell line A549/DDP and its parental cell A549 by miRNAs microarray, of which 14 miRNAs were showed to be significantly (>2-fold) up-regulated and 8 miRNAs had marked down-regulation (<0.5-fold) in A549/DDP cells compared with in A549 cells. MiR-98, a member in the let-7 family, acts as a negative regulator in the expression of HMGA2 (high mobility group A2) oncogene, and it has been shown to have a nearly 3-fold decrease in A549/DDP cells. We found that elevated expression of miR-98 led to a higher sensitivity of A549/DDP cells to cisplatin, and the protein level of HMGA2, was clearly up-regulated in both A549/DDP and A549 cells by miR-98. Moreover, both Bcl-XL and Bcl-2, were down-regulated in the Pre-miR-98(TM) transfectants cells. We for the first time demonstrated that the expression of miR-98 increases cells spontaneous apoptosis and sensitizes cells to cisplatin at least in part via HMGA2 up-regulation. Our findings provided insight into some specific miRNAs in lung cancer as potential therapeutic targets.
authors.affiliation: Institute of Pharmacy and Pharmacology, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Xiang
authors.forename: Huifang
authors.initials: H
authors.lastname: Tang
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Lei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004396:Coloring Agents; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005822:Genetic Vectors; D025743:HMGA2 Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D051020:bcl-X Protein / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D004396:Coloring Agents; D025743:HMGA2 Protein; C546084:MIRN98 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D051020:bcl-X Protein; D008156:Luciferases; C022616:thiazolyl blue; D002945:Cisplatin