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

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 dU...

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Veröffentlicht in:Pharmacogenomics 2019-02, Vol.20 (3), p.155-165
Hauptverfasser: Su, Jiancheng, Ruan, Shaolin, Dai, Shengkun, Mi, Jing, Chen, Wei, Jiang, Songshan
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Sprache:eng
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Zusammenfassung: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 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.
ISSN:1462-2416
1744-8042
DOI:10.2217/pgs-2018-0161