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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2017 | Research

Linc-ROR promotes esophageal squamous cell carcinoma progression through the derepression of SOX9

Authors: Lianghai Wang, Xiaodan Yu, Zhiyu Zhang, Lijuan Pang, Jiang Xu, Jinfang Jiang, Weihua Liang, Yuhang Chai, Jun Hou, Feng Li

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2017

Abstract

Background

Novel therapies tailored to the molecular composition of esophageal squamous cell carcinoma (ESCC) are needed to improve patient survival. We investigated the regulatory network of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) and sex-determining region Y-box 9 (SOX9), and their therapeutic relevance in ESCC.

Methods

Linc-ROR and SOX9 expression were examined in ESCC specimens, cell lines, and cultured tumorspheres. We investigated the effects of linc-ROR on SOX9 expression and malignant phenotypes by CCK8, colony formation, Transwell, and sphere-forming assay. The linc-ROR/SOX9 interaction mediated by multiple microRNAs (miRNAs) was confirmed by bioinformatic analysis, luciferase assay, and RNA-binding protein immunoprecipitation, transient overexpression or antagonizing endogenous candidate miRNAs. The effect of linc-ROR depletion on tumor growth was assessed by xenograft assay.

Results

A positive correlation between linc-ROR and SOX9 expression was found in clinical ESCC specimens (r = 0.562, P = 0.036), cell lines, and tumorspheres. Silencing of linc-ROR significantly inhibited cell proliferation, motility, chemoresistance, and self-renewal capacity. Mechanistically, linc-ROR modulating the derepression of SOX9 by directly sponging multiple miRNAs including miR-15b, miR-33a, miR-129, miR-145, and miR-206. Antagonizing these miRNAs counteracted with linc-ROR silencing, whereas the repression of SOX9 abrogated malignant phenotypes induced by the cocktail of miRNA inhibitors. Moreover, linc-ROR disruption was sufficient to attenuate tumor growth and cancer stem cell marker expression in vivo.

Conclusions

Our results demonstrate that the linc-ROR–miRNA–SOX9 regulatory network may represent a novel therapeutic target for ESCC.

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Title: Linc-ROR promotes esophageal squamous cell carcinoma progression through the derepression of SOX9
Authors: Lianghai Wang
Xiaodan Yu
Zhiyu Zhang
Lijuan Pang
Jiang Xu
Jinfang Jiang
Weihua Liang
Yuhang Chai
Jun Hou
Feng Li
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2017
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-017-0658-2

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