MiR182 Activates the Ras-MEK-ERK Pathway in Human Oral Cavity Squamous Cell Carcinoma by Suppressing RASA1 and SPRED1

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2017 Feb 23

PMID 28223824

Citations 13

Authors

Jinhui Wang

Wei Wang

Jichen Li

Liji Wu

Mei Song

Qinggang Meng

Affiliations

Soon will be listed here.

Abstract

Purpose: The constitutive activation of the Ras-MEK-ERK signaling pathway in oral cavity squamous cell carcinoma (OSCC) has been found to be tightly controlled at multiple levels under physiological conditions. RASA1 and SPRED1 are two important negative regulators of this pathway, but the exact regulating mechanism remains unclear. In this study, we aimed to explore the potential regulating mechanisms involved in the Ras-MEK-ERK signaling pathway in OSCC.

Materials And Methods: MicroRNA (miRNA) expression was detected by quantitative reverse-transcription polymerase chain reaction. The protein levels of RASA1, SPRED1, and signaling proteins were detected by Western blot. Cell growth was determined using CCK-8 reagent, colony formation was stained by crystal violet, and cell invasion was tested using transwell chambers. Cell apoptosis and the cell cycle were then analyzed by flow cytometry. The binding of miR182 with or was evaluated by luciferase reporter assays on a dual-luciferase reporter system.

Results: The expression of miR182 was found to be upregulated significantly in malignant oral carcinoma tissues compared with the adjacent nonmalignant tissues, and was inversely correlated with protein levels of RASA1 and SPRED1. Overexpression of miR182 in OSCC cell lines sustained Ras-MEK-ERK signaling-pathway activation, and promoted cell proliferation, cell-cycle progression, colony formation, and invasion capacity, whereas miR182 downregulation alleviated these properties significantly in vitro. Furthermore, we demonstrated that miR182 exerted its oncogenic role in OSCC by directly targeting and suppressing and .

Conclusion: Our results bring new insights into the important role of miR182 in the activation of the Ras-MEK-ERK signaling pathway, and suggest that miR182 may be used as a potential target for treatment of OSCC, prompting further investigation into miRNA antisense oligonucleotides for cancer therapy.

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