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微小 RNA-655 通过直接靶向黏着斑激酶调节 PTEN/AKT 通路抑制口腔鳞状细胞癌的增殖和侵袭。

MicroRNA‑655 suppresses cell proliferation and invasion in oral squamous cell carcinoma by directly targeting metadherin and regulating the PTEN/AKT pathway.

机构信息

Department of Stomatology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China.

Department of Clinical Medicine, Weifang Medical University, Weifang, Shandong 261053, P.R. China.

出版信息

Mol Med Rep. 2018 Sep;18(3):3106-3114. doi: 10.3892/mmr.2018.9292. Epub 2018 Jul 16.

Abstract

MicroRNAs (miRNAs) are important regulators of a variety of biological processes and their dysregulation is closely related to cancer formation and progression. Therefore, examination of aberrantly expressed miRNAs in oral squamous cell carcinoma (OSCC) may provide important clues for the diagnosis and treatment of patients with OSCC. The aim of the present study was to determine miRNA (miR)‑655‑3p expression in OSCC tissues and cell lines, and to investigate the biological roles and mechanisms of miR‑655‑3p associated with OSCC. Data from the present study indicated that miR‑655 expression was significantly downregulated in human OSCC tissues and cell lines. Overexpression of miR‑655 attenuated cell proliferation and invasion in OSCC in vitro. Metadherin (MTDH) mRNA was predicted as a potential target of miR‑655 by bioinformatics analysis, and this was confirmed by luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis. In OSCC tissues, MTDH was highly expressed and inversely correlated with miR‑655 expression levels. MTDH overexpression reversed the inhibitory effects of miR‑655 mimics in OSCC cells. Notably, the upregulation of miR‑655 expression inhibited the activation of the phosphatase and tensin homolog (PTEN)/RAC‑α serine/threonine‑protein kinase (AKT) pathway in OSCC cells. Therefore, these results may provide the first evidence that miR‑655 targets MTDH to inhibit proliferation and invasion of OSCC by inhibiting PTEN/AKT signaling. Thus, the restoration of miR‑655 expression may be a novel therapeutic strategy for patients with OSCC.

摘要

微小 RNA(miRNAs)是多种生物过程的重要调节因子,其失调与癌症的形成和发展密切相关。因此,研究口腔鳞状细胞癌(OSCC)中异常表达的 miRNAs 可能为 OSCC 患者的诊断和治疗提供重要线索。本研究旨在确定 OSCC 组织和细胞系中 miRNA(miR)-655-3p 的表达,并探讨与 OSCC 相关的 miR-655-3p 的生物学作用和机制。本研究数据表明,miR-655 在人 OSCC 组织和细胞系中的表达明显下调。miR-655 的过表达可减弱 OSCC 细胞在体外的增殖和侵袭。生物信息学分析预测 MTDH mRNA 是 miR-655 的潜在靶标,荧光素酶报告基因检测、逆转录-定量聚合酶链反应和 Western blot 分析对此进行了验证。在 OSCC 组织中,MTDH 高表达且与 miR-655 表达水平呈负相关。MTDH 过表达逆转了 miR-655 模拟物对 OSCC 细胞的抑制作用。值得注意的是,miR-655 表达的上调抑制了 OSCC 细胞中磷酸酶和张力蛋白同源物(PTEN)/ Rac-α 丝氨酸/苏氨酸蛋白激酶(AKT)通路的激活。因此,这些结果可能首次提供证据表明,miR-655 通过抑制 PTEN/AKT 信号通路靶向 MTDH 抑制 OSCC 的增殖和侵袭。因此,恢复 miR-655 的表达可能是 OSCC 患者的一种新的治疗策略。

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