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 |
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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. |
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ISSN: | 1462-2416 1744-8042 |
DOI: | 10.2217/pgs-2018-0161 |