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

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. © 2017 the author(s).