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MicroRNA-101 regulates autophagy, proliferation and apoptosis via targeting EZH2 in laryngeal squamous cell carcinoma

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Lu Chen, Jian Jia, Yanzi Zang, Jing Li,  Baoluo Wan

Abstract:

Laryngeal carcinoma is the second commonest head and neck carcinoma globally. MicroRNA-101 (miR-101) has been reported as a tumor suppressor in multiple malignancies including laryngeal squamous cell carcinoma (LSCC). However, the roles and molecular mechanisms of miR-101 in the development of LSCC have not been fully elucidated. In the present study, RT-qPCR assay was performed to detect the expression of miR-101 and enhancer of zeste homolog 2 (EZH2) mRNA. Western blot assay was conducted to determine protein expression of LC3-I, LC3-II, p62 and EZH2. Cell proliferative capacity was evaluated by MTS assay. The effect of miR-101 alone or along with EZH2 on cell apoptosis was assessed by apoptotic index and caspase-3 activity. Bioinformatic analysis, luciferase assay and RNA immunoprecipitation (RIP) assay were carried out to investigate the interaction between miR-101 and EZH2. Results revealed that miR-101 expression was strikingly down-regulated in LSCC cell lines. Functional analyses showed that ectopic expression of miR-101 suppressed cell autophagy and proliferation and facilitated cell apoptosis in LSCC. Further investigations revealed that miR-101 inhibited EZH2 expression by direct interaction and EZH2 was highly expressed in LSCC cells. Also, EZH2 knockdown reduced the autophagic activity of LSCC cells. Moreover, restoration experiments showed that EZH2 up-regulation weakened miR-101-mediated anti-autophagy, anti-proliferation and pro-apoptosis effects in LSCC cells. In conclusion, our findings suggested that miR-101 inhibited autophagy and proliferation and promoted apoptosis via targeting EZH2 in LSCC, providing a deep insight into the pathogenesis of LSCC and hinting the pivotal roles of epigenetic modifications especially histone methylation in the development of LSCC.

Received date: 08/11/2018

Accepted date: 12/19/2018

Ahead of print publish date: 03/08/2019

Issue: 4/2019

Volume: 66

Pages: 507 — 515

Keywords: Laryngeal squamous cell carcinoma, microRNA-101, EZH2, autophagy, proliferation, apoptosis., microRNA-101, EZH2, autophagy, proliferation, apoptosis.

Supplementary files:
Figure S1 - TE.tif

DOI: 10.4149/neo_2018_180811N611

Pubmed

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