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miR-92a 通过靶向 FOXP1 表达调控口腔鳞状细胞癌(OSCC)细胞生长。

MiR-92a regulates oral squamous cell carcinoma (OSCC) cell growth by targeting FOXP1 expression.

机构信息

Department of Stomatology, Chinese PLA General Hospital, Beijing, 100853, China; Department of Orthodontics, Tianjin Stomatological Hospital (Hospital of Stomatology, Nankai University), Tianjin, 300041, China.

Department of Stomatology, Chinese PLA General Hospital, Beijing, 100853, China.

出版信息

Biomed Pharmacother. 2018 Aug;104:77-86. doi: 10.1016/j.biopha.2018.05.025. Epub 2018 May 14.

Abstract

Increasing evidence indicates that microRNAs dysregulation contributes to the development and progression of various human cancers, including oral squamous cell carcinoma (OSCC). However, little is known about the potential role of microRNA-92a (miR-92a) in OSCC. Thus, the aim of this study was to investigate the effects of miR-92a expression on OSCC cell growth, apoptosis and tumorigenesis. Real-time quantitative polymerase chain reaction was used to detect the expression level of miR-92a in primary tumor tissues and OSCC cell lines. The effects of miR-92a on cell proliferation, cell cycle, apoptosis and tumorigenesis of OSCC cells were explored after miR-92a expression was increased or decreased in the UM1 and Tca-8113 cells, respectively. The 3'-untranslated region (3'-UTR) of FOXP1 combined with miR-92a was analyzed with dual-luciferase reporter assays. The level of miR-92a expression was significantly up-regulated in the OSCC tissues and cell lines. The up-regulation of miR-92a expression promoted UM1 cell proliferation, cell cycle progression in vitro and tumor growth in nude mice, but its expression reduction inhibited these processes and induced apoptosis in Tca-8113 cells. Additionally, miR-92a expression was inversely correlated with FOXP1 protein expression in the OSCC tissues and cell lines. Furthermore, FOXP1 was identified as a functional downstream target of miR-92a by directly targeting the 3'-UTR of FOXP1. These findings indicate that miR-92a may act as a tumor inducer in OSCC by suppressing FOXP1 expression, and it could serve as a potential therapeutic target for OSCC treatment.

摘要

越来越多的证据表明,microRNAs 失调导致了多种人类癌症的发展和进展,包括口腔鳞状细胞癌(OSCC)。然而,miR-92a 在 OSCC 中的潜在作用知之甚少。因此,本研究旨在探讨 miR-92a 表达对 OSCC 细胞生长、凋亡和致瘤性的影响。实时定量聚合酶链反应用于检测原发性肿瘤组织和 OSCC 细胞系中 miR-92a 的表达水平。通过分别增加或降低 UM1 和 Tca-8113 细胞中的 miR-92a 表达,探讨了 miR-92a 对 OSCC 细胞增殖、细胞周期、凋亡和致瘤性的影响。FOXP1 的 3'-非翻译区(3'-UTR)与 miR-92a 结合通过双荧光素酶报告基因检测进行分析。miR-92a 在 OSCC 组织和细胞系中的表达水平显著上调。miR-92a 表达的上调促进了 UM1 细胞的体外增殖、细胞周期进程和裸鼠肿瘤生长,但表达的下调抑制了这些过程并诱导了 Tca-8113 细胞的凋亡。此外,miR-92a 的表达与 OSCC 组织和细胞系中的 FOXP1 蛋白表达呈负相关。此外,FOXP1 被鉴定为 miR-92a 的功能下游靶标,通过直接靶向 FOXP1 的 3'-UTR。这些发现表明,miR-92a 通过抑制 FOXP1 的表达在 OSCC 中可能充当肿瘤诱导物,并且它可以作为 OSCC 治疗的潜在治疗靶点。

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