Department of Nephrology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Department of Ultrasound, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Mol Med Rep. 2019 Jan;19(1):711-718. doi: 10.3892/mmr.2018.9652. Epub 2018 Nov 13.
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.
越来越多的证据表明,微小 RNA(miRNA)是关键的基因调控因子,在透明细胞肾细胞癌(ccRCC)中异常表达。miRNA 的失调与 ccRCC 的发生和发展有关。因此,鉴定与 ccRCC 相关的 miRNAs 可能有助于确定有前途的抗癌治疗靶点。在本研究中,miRNA-663(miR-663)在 ccRCC 组织和细胞系中表达下调。功能实验表明,恢复 miR-663 的表达抑制了 ccRCC 细胞的增殖和侵袭。此外,p21 激活激酶 4(PAK4)被验证为 ccRCC 细胞中 miR-663 的直接靶标。PAK4 在 ccRCC 组织中上调,并且 PAK4 的表达水平与 miR-663 的表达水平呈负相关。PAK4 的恢复部分减弱了 miR-663 过表达对 ccRCC 细胞增殖和侵袭的抑制作用。本研究结果为 ccRCC 发生和发展的机制提供了新的见解,表明 miR-663/PAK4 轴可能是治疗 ccRCC 患者的一种新的治疗靶点。