title: Up-regulation of miR-146a increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J.
abstract: Cisplatin (DDP)-based chemotherapy is the common first-line therapy for lung cancer. However, their efficacy is often limited by primary drug resistance and/or acquired drug resistance. The aim of this study was to investigate the function of miRNA-146a (miR-146a) in DDP-resistant non-small cell lung cancer (NSCLC), as well as the underlying mechanisms.
  
  
  
  The effect of overexpression of miR-146a and/or knockdown of cyclin J (CCNJ) in A549/DDP and SPC-A1/DDP cells were investigated as follows. The cellular sensitivity to DDP, cell apoptosis, cell cycle and cell mobility were detected by CCK-8, flow cytometry, hoechst staining and cell invasion/migration assay, respectively. The effects of miR-146a overexpression in NSCLC resistant cells were further analyzed in a nude mouse xenograft model.
  
  
  
  Overexpression of miR-146a and/or knockdown of CCNJ significantly increased the sensitivity to DDP in A549/DDP and SPC-A1/DDP cells compared to NC group via arresting cell cycle, enhancing cell apoptosis, inhibiting cell viability and motility in vitro and in vivo. Furthermore, miR-146a could specially degrade the mRNA of CCNJ, as examined by dual luciferase report assay.
  
  
  
  The study indicates a crucial role of miR-146a in the development of acquired drug resistance to DDP in NSCLC cells. Further understanding of miR-146a mediated crosstalk networks may promote the clinical use of miR-146a analogue in NSCLC therapy.
authors.affiliation: Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Emergency, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China.
authors.forename: Zhaozhong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Cancer Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Cancer Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of VIP & Traditional Chinese Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yet-sen University, 58 Second Zhongshan Road, Guangzhou, Guangdong, 510080, People's Republic of China. jackhorn@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Ke
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D016213:Cyclins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C000589891:CCNJ protein, human; D016213:Cyclins; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin
keywords: CCNJ; DDP-resistance; NSCLC; miR-146a