title: Let-7c sensitizes acquired cisplatin-resistant A549 cells by targeting ABCC2 and Bcl-XL.
abstract: Cancer cells that develop resistance to cisplatin (DDP) are a major clinical obstacle to the successful treatment of cancer, including non-small cell lung cancer (NSCLC). Recent studies have implicated dysregulation of microRNAs (miRNAs) function in chemoresistance. Here, we explored the role of let-7c in the acquisition of DDP-resistant phenotype in A549 cells. Let-7c was downregulated in A549/DDP cell compared with A549 cells. Modulation of let-7c altered the sensitivity of A549/DDP cells to DDP through regulating DDP-induced apopotis. Furthermore, ABCC2 and Bcl-XL were identified as targets of let-7c. ABCC2 and Bcl-XL knockdown increased DDP sensitivity and DDP-induced apoptosis in A549/DDP cells. In conclusion, our findings suggested for the first time that let-7c modulate DDP response in A549/DDP cells, and one of the mechanisms was through targeting ABCC2 and Bcl-XL. Thus, let-7c could be considered for potential therapeutic application for modulating DDP-based therapy.
authors.affiliation: Institute of Clinical Pharmacology, Central South University, Hunan, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhan
authors.affiliation: Institute of Clinical Pharmacology, Central South University, Hunan, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Qu
authors.affiliation: Institute of Clinical Pharmacology, Central South University, Hunan, PR China.
authors.forename: Guo
authors.initials: G
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Central South University, Hunan, PR China.
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000494:pharmacology*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000187:drug effects*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D051020:bcl-X Protein / Q000187:drug effects*
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D002945:Cisplatin; D005456:Fluorescent Dyes; D035683:MicroRNAs; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012334:RNA, Neoplasm; D051020:bcl-X Protein; C000715087:ABCC2 protein, human; C487931:mirnlet7 microRNA, human; C017807:bisbenzimide ethoxide trihydrochloride