MiRNA-211 triggers an autophagy-dependent apoptosis in cervical cancer cells: regulation of Bcl-2

MiRNA-211 引发宫颈癌细胞自噬依赖性细胞凋亡:调节 Bcl-2

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作者:Shang Liu, Hongyan Wang, Jing Mu, Hao Wang, Yan Peng, Qi Li, Dongwei Mao, Liyuan Guo

Abstract

Cervical cancer is a significant cause of morbidity and mortality in gynecological malignancies. Although autophagy plays a critical role in affecting cell apoptosis and proliferation, the role of hsa-miR-211-5p (miR-211) in modulating autophagy of cervical cancer cells remains unclear. In the current study, the level of miR-211 was downregulated in cervical cancer specimens, compared to the paired para-carcinoma tissues. While Bcl-2 was upregulated, LC3-II/I was decreased in the tumors, indicating inhibited apoptosis and autophagy. The forced expression of miR-211 inhibited proliferation, and promoted apoptosis in SiHa cervical cancer cells, evidenced by increased expression of apoptotic proteins, caspase-3, and PARP. While the miR-211 inhibitor exerted reverse effects on C-33A cervical cancer cells. Further, miR-211 induced autophagy in cervical cancer cells, as manifested by the presence of LC3 puncta, increased LC3-II/I and Beclin1 levels, and decreased p62 level. The miR-211-induced apoptosis was alleviated by an autophagy inhibitor 3-methyladenine (3-MA). In addition, Bcl-2 was identified as a target of miR-211. Besides, the apoptosis and autophagy triggered by miR-211 were attenuated by Bcl-2 in SiHa cells. In summary, our work indicates that miR-211 induced autophagy and autophagy-dependent apoptosis by regulating Bcl-2 in cervical cancer cells, which provided further understanding of autophagy in cervical carcinogenesis.

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