Oncotarget

Research Papers:

miR-675-5p enhances tumorigenesis and metastasis of esophageal squamous cell carcinoma by targeting REPS2

Yan-Wu Zhou, Hang Zhang, Chao-Jun Duan, Yang Gao, Yuan-Da Cheng, Dan He, Rong Li and Chun-Fang Zhang _

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Oncotarget. 2016; 7:30730-30747. https://doi.org/10.18632/oncotarget.8950

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Abstract

Yan-Wu Zhou1, Hang Zhang1, Chao-Jun Duan2, Yang Gao1, Yuan-Da Cheng1, Dan He2, Rong Li3, Chun-Fang Zhang1

1Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China

2Institute of Medical Science, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China

3Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China

Correspondence to:

Chun-Fang Zhang, e-mail: [email protected]

Keywords: miR-675-5p, REPS2, esophageal squamous cell carcinoma, microRNA, RAC1/CDC42

Received: November 08, 2015     Accepted: April 08, 2016     Published: April 23, 2016

ABSTRACT

Recently H19 has been demonstrated to be up-regulated in esophageal squamous cell carcinoma (ESCC) and shown to be the precursor of miR-675 that encodes miR-675-5p conservatively. miR-675 is overexpressed in many human cancers; however, the function of miR-675-5p is largely unknown in ESCC. In this study, we found that miR-675-5p expression was significantly increased in ESCC tissues and cell lines and related with ESCC progression and poor prognosis. We also showed here that down-regulation of miR-675-5p in ESCC cells dramatically induced cell G1 arrest and reduced cell proliferation, colony formation, migration and invasion in vitro as well as tumorigenesis and tumor metastasis in vivo. We subsequently identified that REPS2 was a target gene of miR-675-5p. We found that inhibition of miR-675-5p up-regulated the expression of REPS2, inhibited RalBP1/RAC1/CDC42 signaling pathway. Inversely, interference of REPS2 abrogated the effect induced by miR-675-5p inhibition, which resembled the function of miR-675-5p up-regulation. Taken together, our findings suggested that miR-675-5p might play an oncogenic role in ESCC through RalBP1/RAC1/CDC42 signaling pathway by inhibiting REPS2 and might serve as a valuable prognostic biomarker and therapeutic target for ESCC patients.


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