title: Downregulation of miR-21 increases cisplatin sensitivity of non-small-cell lung cancer.
abstract: Recent studies have shown that plasma miR-21 is a biomarker of chemotherapeutic response in lung cancer, but the influence of miR-21 on the sensitivity of non-small-cell lung cancer (NSCLC) to cisplatin (DDP) has not been confirmed. The aim of this study was to evaluate the role of miR-21 in NSCLC sensitivity to DDP in vitro and in vivo. Real-time quantitative PCR was used to detect miR-21 expression in lung cancer cell lines. Synthesized locked nucleic acid (LNA) anti-miR-21 was transiently transfected into A549 cells and pre-miR-21 was transfected into SK-MES-1 cells. We also investigated the effects of miR-21 downregulation and upregulation on growth and colony formation in DDP-treated cells. Finally, the effect of miR-21 downregulation on in vivo sensitivity of A549 cells to DDP was determined in BALB/c nude mice. miR-21 expression was significantly higher in A549 than in other lung cancer cell lines. LNA-based knockdown of miR-21 significantly inhibited growth and induced death in A549 cells, possibly via apoptotic signaling. Pre-miR-21 significantly promoted growth and inhibited death in SK-MES-1 cells. Moreover, ectopic suppression of miR-21 sensitized A549 cells to DDP in vivo. Our findings demonstrate that miR-21 suppression enhances the sensitivity of lung cancer cells to DDP in vitro and in vivo.
authors.affiliation: Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhejiang, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Xu
authors.affiliation: Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhejiang, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhejiang, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhejiang, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: He
authors.affiliation: Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhejiang, China.
authors.forename: Wangyu
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Cardio-Thoracic surgery, Zhoushan Hospital, Zhejiang, China. Electronic address: zyk801801@126.com.
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhejiang, China. Electronic address: lxg2004@gmail.com.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D055786:Gene Knockout Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009841:Oligonucleotides / Q000235:genetics; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; C477371:locked nucleic acid; D002945:Cisplatin
keywords: A549; LNA anti–miR-21; chemotherapy; cisplatin; lung cancer