NF1 Regulates Apoptosis in Ovarian Cancer Cells by Targeting MCL1 via miR-142–5p

Abstract

Aim: 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. Materials & methods: 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. Results: 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. Conclusion: NF1 knockdown endowed ovarian cells with resistance to cisplatin-induced apoptosis by targeting MCL1 via miR-142-5p.

Keywords::

• apoptosis
• MCL1
• miR-142-5p
• NF1
• ovarian cancer

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.futuremedicine.com/doi/suppl/10.2217/pgs-2018-0161

Financial & competing interests disclosure

This study was supported by grants from the Natural Science Foundation of Guangdong Province (grant no. 2017A030313656), the Special Funds for the Cultivation of Guangdong College Students’ Scientific and Technological Innovation (grant no. pdjh2017b0014) and the Natural Science Foundation of China (grant no. 81572567). The authors declare that no conflicts of interests exist. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. Furthermore, informed consent has been obtained from the participants involved for investigations involving human subjects.

Author’s contributions

J Su, S Ruan, S Dai, J Mi and W Chen performed experiments; J Su, S Ruan, S Dai, W Chen, J Mi and S Jiang designed the research and analyzed the data; S Ruan and S Jiang drafted the manuscripts and all authors commented on it; J Su and S Ruan made equal contributions to the study; and S Jiang coordinated the project.

Additional information

Funding

Financial & competing interests disclosure This study was supported by grants from the Natural Science Foundation of Guangdong Province (grant no. 2017A030313656), the Special Funds for the Cultivation of Guangdong College Students’ Scientific and Technological Innovation (grant no. pdjh2017b0014) and the Natural Science Foundation of China (grant no. 81572567). The authors declare that no conflicts of interests exist. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript.