miR‑92b promotes autophagy and suppresses viability and invasion in breast cancer by targeting EZH2

miR-92b 通过靶向 EZH2 促进自噬并抑制乳腺癌的生存和侵袭

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作者:Fei Liu, Meixiang Sang, Lingjiao Meng, Lina Gu, Shina Liu, Juan Li, Cuizhi Geng

Abstract

MicroRNAs (miRs) are a small non-coding RNA family with a length of 18-22 nucleotides. They are able to regulate gene expression by either triggering target messenger RNA degradation or by inhibiting mRNA translation. Enhancer of zeste homolog 2 (EZH2) is the core enzymatic subunit of polycomb repressor complex 2 and is responsible for the trimethylation of histone 3 on lysine 27 (H3K27me3); it is also able to silence a bundle of tumor suppressor genes through promoter binding. However, little is known regarding the effect of miR‑92b on cell autophagy, viability and invasion as well as how it interacts with EZH2. The present study investigated the major role of miR‑92b in the autophagy, viability and invasion of breast cancer. It was revealed that in MCF‑7 and MDA‑MB‑453 cells, the expression of miR‑92b promoted autophagy induced by starvation and rapamycin treatment. The results of in vitro experiments results demonstrated that miR‑92b inhibited breast cancer cell viability, invasion and migration. To further elucidate the regulatory mechanisms of miR‑92b in autophagy, a dual luciferase reporter assay was performed to determine whether miR‑92b targeted the EZH2 gene. The expression of miR‑92b was negatively correlated to EZH2 mRNA expression in breast cancer. Depletion of EZH2 induced phenocopied effects on miR‑92b overexpression, thereby demonstrating its importance in autophagy. These results indicated that miR‑92b may serve an important role in breast cancer in controlling autophagy, viability and invasion. The present study indicated that miR‑92b and EZH2 may serve as potential biomarkers for cancer detection and highlighted their possible therapeutic implications.

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