2018Molecular Medicine ReportsOpen access

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

Ying‐Ying Liu, Dan Jiao, Zhen Tian

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Abstract

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.

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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.

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Available abstract

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.

Key concepts: Clear cell renal cell carcinoma, Oncogene, microRNA, Cancer research, Cell growth, Cell cycle, Biology, Cell

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