miR-34a sensitizes lung cancer cells to cisplatin via p53/miR-34a/MYCN axis.
Cisplatin is the most potent and widespread used chemotherapy drug for lung cancer treatment. However, a large proportion of NSCLC patients were insensitive to chemotherapy. This study explored the role of miR-34a in regulating sensitivity of NSCLC cells to cisplatin and its downstream targets. The quantitative PCR result showed that miR-34a expression was upregulated in cisplatin sensitive NSCLC patients compared cisplatin insensitive NSCLC controls. By applying loss-and-gain function analysis, we demonstrated that miR-34a directly targeted to MYCN to sensitize NSCLC cells to cisplatin. In addition, p53 was found to monitor the expression of miR-34a in NSCLC cells after cisplatin treatment. Therefore, the sensitivity of cisplatin in NSCLC cells was modulated via p53/miR-34a/MYCN axis.
Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, China.
Changshan
C
Song
Department of Thoracic Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.
Pingfang
P
Lu
Department of Thoracic Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.
Guoqiang
G
Sun
Department of Thoracic Surgery, 2nd Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, China.
Lin
L
Yang
Department of Thoracic Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. Electronic address: squarelu@163.com.
Zhigang
Z
Wang
Department of Thoracic Surgery, 2nd Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, China. Electronic address: 393189952@qq.com.
Zheng
Z
Wang
D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D000071447:N-Myc Proto-Oncogene Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000970:Antineoplastic Agents; C522425:MIRN34 microRNA, human; C459801:MYCN protein, human; D035683:MicroRNAs; D000071447:N-Myc Proto-Oncogene Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin
Cisplatin; MYCN; NSCLC; miR-34a; p53