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06 October 2017 : Laboratory Research  

Downregulation of lncRNA X Inactive Specific Transcript (XIST) Suppresses Cell Proliferation and Enhances Radiosensitivity by Upregulating mir-29c in Nasopharyngeal Carcinoma Cells

Qian Han1BD, Liang Li1AC, Hengpo Liang1AE*, Yaqiong Li1CE, Jiacun Xie1DF, Zhibin Wang1BF

DOI: 10.12659/MSM.905370

Med Sci Monit 2017; 23:4798-4807

Abstract

BACKGROUND: LncRNA X inactive specific transcript (XIST) was reported to function as an oncogene in nasopharyngeal carcinoma cells (NPC) by sponging miR-34a-5p. However, the role of XIST in modulating the radiosensitivity of NPC cells and its mechanism still remain undefined.

MATERIAL AND METHODS: The expressions of XIST and miR-29c in NPC cells were evaluated by qRT-PCR. CNE1 and CNE2 cells were transfected with si-XIST, pcDNA-XIST, miR-29c mimics, anti-miR-29c, or respective controls by Lipofectamine 2000. The effects of XIST knockdown and miR-29c overexpression on cell proliferation, survival fraction, and γ-H2AX expression were investigated by CCK-8 assay, colony formation assay, immunofluorescence, and Western blot, respectively. Luciferase reporter assay and qRT-PCR analysis were performed to confirm whether XIST interacts with miR-29c and regulates its expression.

RESULTS: XIST was upregulated and miR-29c was downregulated in NPC cells. The expressions of XIST and miR-29c changed reversely in response to irradiation. Knockdown of XIST and miR-29c overexpression both resulted in a dramatic suppression of cell proliferation, a marked enhancement of radiosensitivity, and an obvious increase of γ-H2AX foci formation in NPC cells. Luciferase reporter assay and qRT-PCR analysis demonstrated that XIST interacts with miR-29c and negatively regulates its expression. Moreover, miR-29c inhibition abrogated XIST knockdown-induced cell proliferation inhibition and radiosensitivity increase in NPC cells.

CONCLUSIONS: XIST knockdown suppressed cell proliferation and enhanced radiosensitivity of NPC cells by upregulating miR-29c, providing a novel therapeutic target to improve radiotherapy efficiency for patients with NPC.

Keywords: Radiation Tolerance

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750