Mechanism of Epithelial‑mesenchymal Transition Inhibited by MiR‑203 in Non‑small Cell Lung Cancer

Overview

Journal Oncol Rep

Specialty Oncology

Date 2020 Jan 3

PMID 31894278

Citations 7

Authors

Weicong Huang

Yuanbo Wu

Dezhi Cheng

Zhifeng He

Affiliations

Soon will be listed here.

Abstract

The aim of the present study was to investigate whether miR‑203 can inhibit transforming growth factor‑β (TGF‑β)‑induced epithelial‑mesenchymal transition (EMT), and the migration and invasion ability of non‑small cell lung cancer (NSCLC) cells by targeting SMAD3. In the present study, the expression levels of miR‑203, SMAD3 mRNA and protein in NSCLC tissues were examined, as well as their corresponding paracancerous samples. The miR‑203 mimics and miR‑203 inhibitor were transfected into the H226 cell line. RT‑qPCR was used to assess the expression levels of E‑cadherin, Snail, N‑cadherin and vimentin mRNA, and western blotting was performed to detect the expression levels of p‑SMAD2, SMAD2, p‑SMAD3, SMAD3 and SMAD4. The cell migration and invasion abilities were detected by Transwell assays. The target site of SMAD3 was predicted by the combined action between miR‑203 and dual luciferase. The results revealed that the RNA levels of miR‑203, compared with paracancerous tissues, were decreased in NSCLC tissues, while SMAD3 mRNA and protein levels were upregulated, and miR‑203 inhibited SMAD3 expression. Induction of TGF‑β led to decreased E‑cadherin mRNA levels, upregulation of Snail, N‑cadherin and vimentin mRNA levels (P<0.05), and significant increase in cell migration and invasion, whereas transfection of miR‑203 mimics reversed the aforementioned results (P<0.05). Conversely, miR‑203 inhibitor could further aggravate the aforementioned results (P<0.05). Western blot results revealed that transfection of miR‑203 mimics significantly reduced the protein expression of SMAD3 and p‑SMAD3 (P<0.05). Furthermore, the results of the Dual‑Luciferase assay revealed that miR‑203 inhibited SMAD3 expression by interacting with specific regions of its 3'‑UTR. Overall, a novel mechanism is revealed, in which, miR‑203 can inhibit SMAD3 by interacting with specific regions of the 3'‑UTR of SMAD3, thereby restraining TGF‑β‑induced EMT progression and migration and invasion of NSCLC cells.

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