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口腔鳞状细胞癌中 microRNA 99a 的下调促进口腔癌细胞的生长和存活。

Downregulation of microRNA 99a in oral squamous cell carcinomas contributes to the growth and survival of oral cancer cells.

机构信息

Department of Oral and Maxillofacial Surgery, Ningbo First Hospital, Ningbo 315000, PR China.

出版信息

Mol Med Rep. 2012 Sep;6(3):675-81. doi: 10.3892/mmr.2012.971. Epub 2012 Jun 27.

Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by either translational inhibition or mRNA degradation. miRNAs play pivotal roles in physiological functioning and pathological progression. The function of microRNA-99a (miR-99a) in oral squamous cell carcinoma (OSCC) remains unclear. In the present study, we investigated the roles of miR-99a in OSCC development and the underlying mechanisms in 25 cases of primary OSCC tissues and Tca-8113 cells. The cells were analyzed using FACS analysis and western blotting. Results showed that the expression levels of miR-99a were markedly decreased in OSCC tissues compared with the adjacent non-tumor tissues (n=25). The results of in vitro experiments showed that miR-99a mimics significantly inhibited the proliferation of Tca-8113 cells, a tongue squamous carcinoma cell line, and that miR-99a mimics markedly induced the apoptosis of Tca-8113 cells. Furthermore, we demonstrated that mammalian target of rapamycin (mTOR) was directly targeted by miR-99a, as the overexpression of miR-99a in Tca-8113 cells downregulated the protein expression level of mTOR. Thus, our findings suggest that the downregulation of miR-99a in OSCC tissues is associated with tumor development. miR-99a regulates the growth and survival of OSCC cells and may be exploited as a biomarker and therapeutic target for patients with OSCC.

摘要

微小 RNA(miRNA)是一种小的非编码 RNA 分子,通过翻译抑制或 mRNA 降解来调节基因表达。miRNA 在生理功能和病理进展中发挥着关键作用。miRNA-99a(miR-99a)在口腔鳞状细胞癌(OSCC)中的作用尚不清楚。在本研究中,我们研究了 miR-99a 在 25 例原发性 OSCC 组织和 Tca-8113 细胞中的 OSCC 发展和潜在机制中的作用。使用 FACS 分析和 Western blot 分析对细胞进行分析。结果表明,与相邻非肿瘤组织(n=25)相比,OSCC 组织中 miR-99a 的表达水平明显降低。体外实验结果表明,miR-99a 模拟物显著抑制舌鳞癌细胞系 Tca-8113 细胞的增殖,并且 miR-99a 模拟物明显诱导 Tca-8113 细胞的凋亡。此外,我们证明了雷帕霉素靶蛋白(mTOR)是 miR-99a 的直接靶标,因为 Tca-8113 细胞中 miR-99a 的过表达下调了 mTOR 的蛋白表达水平。因此,我们的研究结果表明,OSCC 组织中 miR-99a 的下调与肿瘤的发生有关。miR-99a 调节 OSCC 细胞的生长和存活,可作为 OSCC 患者的生物标志物和治疗靶点。

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