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Linc‐ROR regulates apoptosis in esophageal squamous cell carcinoma via modulation of p53 ubiquitination by targeting miR‐204‐5p/MDM2

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The long intergenic noncoding RNA, regulator of reprogramming (linc‐ROR) has been reported to participate in tumorigenesis, while its functions and fundamental mechanisms in esophageal squamous cell carcinoma (ESCC) remain unclear.… Click to show full abstract

The long intergenic noncoding RNA, regulator of reprogramming (linc‐ROR) has been reported to participate in tumorigenesis, while its functions and fundamental mechanisms in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, gain‐of‐function assays showed that linc‐ROR upregulation enhanced cell viability, promoted cell proliferation, and inhibited apoptosis. Mechanistically, the regulatory network of linc‐ROR/miR‐204‐5p/MDM2 was established with bioinformatics analysis and online databases, then validated via dual‐luciferase reporter assays, RNA immunoprecipitation assays in ESCC cells. Linc‐ROR positively regulates the expression of MDM2 as a molecular sponge of miR‐204‐5p. Moreover, results of western blot and coimmunoprecipitation indicated that linc‐ROR overexpression enhanced the ubiquitination level of p53, and its downstream apoptosis‐related genes have showed higher bcl‐2 expression, lower bax, and cleaved caspase‐3 expressions, while miR‐204‐5p could counteract with this effect. Finally, small interfering RNAs tailored to linc‐ROR were established to further evaluate its effects on ESCC comprehensively. In summary, this study revealed that linc‐ROR modulated cell apoptosis and regulated p53 ubiquitination via targeting miR‐204‐5p/MDM2 axis, which provides a novel therapeutic insight into treatments for ESCC.

Keywords: esophageal squamous; ror; linc ror; 204 mdm2; mir 204; cell

Journal Title: Journal of Cellular Physiology
Year Published: 2019

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