Resveratrol Suppresses Human Nasopharyngeal Carcinoma Cell Growth Via Inhibiting Differentiation Antagonizing Non-Protein Coding RNA (DANCR) Expression

白藜芦醇通过抑制分化拮抗非蛋白编码 RNA (DANCR) 表达来抑制人类鼻咽癌细胞生长

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作者:Jiafeng Zhang, Xiaojie Jin, Chuan Zhou, Hui Zhao, Ping He, Yalin Hao, Qiongna Dong

Abstract

BACKGROUND Although resveratrol has been found to show anti-cancer effects and potential chemotherapeutic activities in several cancers, the role and molecular mechanisms of resveratrol in nasopharyngeal carcinoma (NPC) remains poorly understood. This study aimed to investigate the effect of resveratrol in NPC progression and its molecular mechanism. MATERIAL AND METHODS Quantitative real-time polymerase chain reaction and western blotting were used to detect the expression of DANCR and PTEN. MTT assay and EdU assay were performed to detect the cell proliferation in NPC cells with different treatment. The effect of resveratrol on cell migration was explored by Transwell migration assay. RNA immunoprecipitation assay and chromatin immunoprecipitation assay were performed to test the interaction between DANCR, EZH2, and PTEN. A mouse xenograft model of NPC cell was established, and immunohistochemistry assay was performed to detect the PTEN expression. RESULTS Resveratrol treatment inhibited NPC cell growth and migration in a dose-dependent manner. Additionally, resveratrol downregulated the expression of DANCR and DANCR overexpressing abrogated the inhibition effect of resveratrol on NPC cell migration. Mechanistically, DANCR could bind to EZH2 and downregulated PTEN expression through mediating the binding of EZH2 on PTEN promoter. Furthermore, rescue experiments suggested resveratrol inhibited NPC cell growth and migration by the DANCR/PTEN pathway. Resveratrol significantly decreased the tumor volume and tumor weight and increased the expression of PTEN. CONCLUSIONS Resveratrol increased PTEN expression and suppressed NPC cell growth and migration through downregulation of DANCR.

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