The miR‐140‐5p/KLF9/KCNQ1 axis promotes the progression of renal cell carcinoma

Although renal cell carcinoma (RCC) is a common malignant urological cancer, its pathogenesis remains unclear. Previous studies have indicated that miR‐140‐5p acts as a tumor suppressor in various tumors, including bladder cancer, hepatocellular carcinoma, and gastric cancer, but its biological function in RCC remains unknown. In the present study, we found that miR‐140‐5p was upregulated in RCC tissues, whereas Krüppel‐like factor 9 (KLF9) was downregulated and correlated inversely with miR‐140‐5p in RCC tissues. miR‐140‐5p promoted the proliferation, migration, and invasion of RCC cells in vitro, and knockdown of miR‐140‐5p significantly suppressed tumor growth and lung metastasis in nude mouse model of RCC. We also found that miR‐140‐5p significantly suppressed the expression of KLF9 by binding to the 3ʹ‐UTR of KLF9 mRNA and that KLF9, as a transcription factor, upregulates KCNQ1 (also called Kv7.1 and KvLQT1) expression by binding to the site (−841/−827) in the KCNQ1 promoter region in RCC cells. Moreover, forced expression of KCNQ1 decreased the growth and metastasis of RCC cells. These results suggest that the miR‐140‐5p/KLF9/KCNQ1 axis functions as a key signaling pathway in RCC progression and metastasis and represents a potential target of RCC therapies.