Three LHPP gene‐targeting co‐expressed microRNAs (microRNA‐765, microRNA‐21, and microRNA‐144) promote proliferation, epithelial‐mesenchymal transition, invasion, and are independent prognostic biomarkers in renal cell carcinomas patients

BACKGROUND: Renal cell carcinoma (RCC) is one of the highly malignant tumors in the world. Global Cancer Statistics 2020 estimated that there were 179,368 deaths from kidney tumors. Therefore, exploring the prognostic biomarkers of RCC is of great significance for RCC patients. This study aims to explore the potential mechanism and prognostic value of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) gene‐targeting co‐expression microRNAs in RCC patients. METHODS: A total of 60 RCC patients were included. Quantitative real‐time PCR (qRT‐PCR), western blotting, and immunohistochemistry were used for LHPP, microRNA‐765, microRNA‐21, and microRNA‐144 levels evaluation. Cell Counting Kit‐8 assay, dual‐luciferase reporter gene assay, invasion assay, and RNA fluorescence in situ hybridization were used for functional analyses. RESULTS: Compared with adjacent tissues, LHPP levels in cancer tissues were significantly increased (p < .001). Herein, we confirmed that microRNA‐765, microRNA‐21, and microRNA‐144 were direct biological targets of LHPP. MicroRNA‐765 (r = −0.570, p < 0.001), microRNA‐21 (r = −0.495, p < .001), and microRNA‐144 (r = −0.463, p < .001) expression levels were negatively correlated with LHPP expression levels. The high expression levels of microRNA‐765, microRNA‐21, and microRNA‐144 in RCC tissues were associated with poor differentiation, recurrence, and poor prognosis (p < .05). In vitro, microRNA‐765, microRNA‐21, and microRNA‐144 act as oncogenes to promote proliferation, invasion, and epithelial‐mesenchymal transition (EMT) through targeting LHPP. CONCLUSIONS: MicroRNA‐765, microRNA‐21, and microRNA‐144 are independent risk biomarkers for RCC patients. Inhibiting the expression levels of microRNA‐765, microRNA‐21, and microRNA‐144 can reduce the proliferation, EMT, and invasion of RCC cells. Therefore, the above three microRNAs are expected to become molecular biomarkers for RCC therapy.