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

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.

Long Non-Coding RNA PCED1B-AS1 Promotes the Progression of Clear Cell Renal Cell Carcinoma Through miR-484/ZEB1 Axis

“…12 Aberrantly expressed miRNAs participate in the growth and metastasis of ccRCC. [13][14][15][16] For example, miR-663 is down-regulated in ccRCC tissues and cell lines, and miR-663 can directly target PAK4 to impede the proliferation and invasion of ccRCC cells. 15 Additionally, in ccRCC, miR-124 and miR-203 participate in the activation of the epithelial-mesenchymal transition (EMT) pathway by regulating ZEB2.…”

“…[13][14][15][16] For example, miR-663 is down-regulated in ccRCC tissues and cell lines, and miR-663 can directly target PAK4 to impede the proliferation and invasion of ccRCC cells. 15 Additionally, in ccRCC, miR-124 and miR-203 participate in the activation of the epithelial-mesenchymal transition (EMT) pathway by regulating ZEB2. 16 Accumulating studies show that lncRNA can function as a competitive endogenous RNA (ceRNA) to regulate downstream gene expression at the post-transcriptional level by sponging miRNAs.…”

PAK4, a target of miR-9-5p, promotes cell proliferation and inhibits apoptosis in colorectal cancer

“…They have been shown to mediate translational repression and target mRNAs for degradation, predominantly by binding to the 3′-untranslated regions (3′-UTRs) in a sequence-specific manner [18]. PAK4 has been reported to be target regulated by miR-433 in hepatocellular carcinoma [19], miR-224 in gastric cancer [20], miR-485 in glioblastoma [21], miR-199a-3p in gastric cancer [22] and hepatocellular carcinoma [23], and miR-663 in clear cell renal cell carcinoma [24].…”