MiRNA-211 triggers an autophagy-dependent apoptosis in cervical cancer cells: regulation of Bcl-2
- Naunyn Schmiedebergs Arch Pharmacol. 2020 Mar;393(3):359-370. doi: 10.1007/s00210-019-01720-4.
- 1. Department of Gynecology, Cancer Hospital of Harbin Medical University, 150 Haping Road, Harbin, 150081, People's Republic of China.
- 2. Disease Prevention Center, Heilongjiang University of Chinese Medicine, Harbin, 150040, People's Republic of China.
- 3. Department of Gynecology, Shenzhen Hospital, Guangzhou University of Chinese Medicine, Shenzhen, 518034, People's Republic of China.
- 4. Department of Gynecology, Cancer Hospital of Harbin Medical University, 150 Haping Road, Harbin, 150081, People's Republic of China. [email protected].
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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Research Areas: Cancer