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

Abstract

BackgroundLncRNA 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/MethodsThe 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.ResultsXIST 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.ConclusionsXIST 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.

miR‐142‐5p protects against osteoarthritis through competing with lncRNA XIST

“…Through bioinformatics analysis and experimental results, we identified lncRNA XIST as a sponge of miR‐142‐5p. XIST widely exerts oncogenic properties in lung adenocarcinoma, nasopharyngeal carcinoma and colorectal cancer . In the present study, we first found the association of XIST with miR‐142‐5p in OA.…”

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

“…In the past 5 years, the mechanism of lncRNA and miRNA in the progression, radioresistance, drug resistance, and angiogenesis of NPC has been studied. 184,[205][206][207] The role of lncRNAs and miRNAs in different NPC cell lines and the corresponding mechanisms have been, respectively, listed in Tables 1 and 2. The anti-cancer effect Recent studies have found that some microRNAs and lncRNAs in tumor tissues are downregulated and show negative regulation of pathological activities of NPC.…”

“…The knockdown of lncRNA X inactive-specific transcript (XIST) could upregulate miR-29c, resulting in the inhibition of DNA damage repair and an increase of the radiosensitivity of NPC cells. 206 Antidifferentiation non-coding RNA (ANCR) could regulate PTEN expression epigenetically to promote radioresistance. 226 Besides, lncRNA MALAT1 modulates cancer stem cell activity of NPC and induces radioresistance via regulating the miR-1/slug axis.…”

Thermal pretreatment promotes the protective effect of HSP70 against tendon adhesion in tendon healing by increasing HSP70 expression

“…Next, the fluorescent intensity was observed and photographed under a fluorescence inverted microscope (magnification, ×200; CX41-12C02, Olympus Optical Co., Ltd., Tokyo, Japan) following 48 h transfection. The transfection efficiency was calculated according to the following formula: Transfection efficiency (%) = number of cells with green fluorescent protein (GFP)/total cell number ×100% (17,18). A total of 5 high-power fields were randomly selected, and the mean values were determined.…”