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MicroRNA-663 inhibits the proliferation and invasion of clear cell renal cell carcinoma cells by directly targeting PAK4

机译:MicroRNA-663通过直接瞄准PAK4抑制透明细胞肾细胞癌细胞的增殖和侵袭

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摘要

Accumulating evidence has demonstrated that microRNAs (miRNAs) are key gene regulators and are abnormally expressed in clear cell renal cell carcinoma (ccRCC). The dysregulation of miRNAs has been implicated in the initiation and progression of ccRCC. Therefore, identification of ccRCC-associated miRNAs may facilitate the determination of promising therapeutic targets for anti-cancer treatment. In the present study, miRNA-663 (miR-663) expression was downregulated in ccRCC tissues and cell lines. Functional experiments suggested that restoration of miR-663 expression inhibited the proliferation and invasion of ccRCC cells. In addition, p21 activated kinase 4 (PAK4) was validated as a direct target of miR-663 in ccRCC cells. PAK4 was upregulated in ccRCC tissues, and the expression level of PAK4 was inversely correlated with the miR-663 expression level. PAK4 restoration partially attenuated the suppressive roles of miR-663 overexpression on the proliferation and invasion of ccRCC cells. The present results provide novel insight into the mechanism underlying the occurrence and development of ccRCC, suggesting that the miR-663/PAK4 axis may be a novel therapeutic target for treatment of patients with ccRCC.
机译:越来越多的证据表明,微RNA(miRNA)是关键基因监管机构和在透明细胞肾细胞癌(肾透明细胞癌)的异常表达。 miRNA的失调有牵连的肾透明细胞癌的发生和发展。因此,肾透明细胞癌相关的miRNA的鉴定可以促进有希望的治疗靶标用于抗癌治疗的确定。在本研究中,miRNA的-663(MIR-663)的表达在肾透明细胞癌组织和细胞系中被下调。功能实验显示的miR-663表达的该恢复抑制肾透明细胞癌的细胞的增殖和侵袭。另外,p21的活化激酶4(PAK4)被验证为的miR-663的在肾透明细胞癌细胞的直接靶标。 PAK4被上调在肾透明细胞癌组织和PAK4的表达水平呈负所述miR-663的表达水平相关。 PAK4恢复部分减弱肾透明细胞癌上的细胞的增殖和侵袭的miR-663过表达的抑制的作用。本发明的结果提供新颖的洞察肾透明细胞癌的发生和发展的基础的机制,这表明所述miR-663 / PAK4轴可以是一种新的治疗靶标用于治疗患有肾透明细胞癌。

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