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PMID: 30543142 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

NF1 regulates apoptosis in ovarian cancer cells by targeting MCL1 via miR-142-5p.

Pharmacogenomics ·Vol. 20 ·No. 3 ·2019-00-00 ·页码 155-165

Su J, Ruan S, Dai S, Mi J, Chen W, Jiang S

Abstract

NF1 loss confers chemoresistance in multiple cancers. However, the etiology remains largely unknown. Our study aimed to scrutinize the role of NF1 in chemoresistant ovarian cancer and its underlying mechanism. 4',6-diamidino-2-phenylindole staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, luciferase reporter assay, chromatin immunoprecipitation, Western blot, quantitative real-time-PCR and rescue experiments were performed to illustrate the antiapoptotic role of NF1 loss and its underlying mechanism. NF1-knockdown ovarian cells showed resistance to cisplatin-induced apoptosis. Furthermore, NF1 regulated MCL1 expression at protein level. Further dissections suggested that miR-142-5p was regulated by NF1 via its promoter and targeted MCL1. Consistently, miR-142-5p mimic and si-MCL1 can attenuate the antiapoptotic effect of NF1 knockdown. NF1 knockdown endowed ovarian cells with resistance to cisplatin-induced apoptosis by targeting MCL1 via miR-142-5p.

Keywords
apoptosis miR-142-5p ovarian cancer
MeSH 主题词
Apoptosis/drug effects Cell Line, Tumor Cisplatin/adverse effects,pharmacology Drug Resistance, Neoplasm/genetics Female Gene Knockdown Techniques Humans MicroRNAs/genetics Myeloid Cell Leukemia Sequence 1 Protein/genetics Neurofibromin 1/genetics Ovarian Neoplasms/drug therapy,genetics,pathology
化学物质
MCL1 protein, human MIRN142 microRNA, human MicroRNAs Myeloid Cell Leukemia Sequence 1 Protein NF1 protein, human Neurofibromin 1 Cisplatin
作者与单位
共 6 位作者,点击展开单位 / ORCID
Su Jiancheng
Department of Biological Sciences & Technology, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.
Ruan Shaolin
Department of Biological Sciences & Technology, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.
Dai Shengkun
Department of Biological Sciences & Technology, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.
Mi Jing
Department of Biological Sciences & Technology, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.
Chen Wei
Department of Gynecology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR China.
Jiang Songshan
Department of Biological Sciences & Technology, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.
Article Info
Journal
Pharmacogenomics
Abbr.
Pharmacogenomics
ISSN
1744-8042
Published
2019-00-00
电子出版
2018-00-13
页码
155-165
Language
English
Country/Region
England
NLM ID
100897350
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