The Role of miR-181a-5p and its Target Genes in the Progression of Clear Cell Renal Cell Carcinoma and Association With the Immune Microenvironment.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most predominant pathological types of renal cell carcinoma (RCC), with a high metastatic rate and poor prognosis. There is growing appreciation that miR-181a-5p plays a crucial role in various cancers, but the relevance of miR-181a-5p to disease progression in ccRCC and its mechanism of action in ccRCC remain poorly reported in detail. This study purposed to explore new biomarkers related to the prognosis of ccRCC and to uncover their potential mechanisms in influencing ccRCC progression.

Methods: The dbDEMC and GEO databases were used to screen differential miRNAs and differential genes in ccRCC, respectively. KEGG pathway analysis was performed to further search for differential genes in ccRCC. The miRWalk database was used to predict target genes of miR-181a-5p. The miR-181a-5p and its target genes expression, clinicopathological correlation, prognosis analysis, and immune infiltration correlation were performed in the data obtained from TCGA. STRING database was performed to construct a PPI network of the target genes of miR-181a-5p and immune-related genes of ccRCC from TISIBD database. In vitro experiments were conducted to verify the effect of miR-181a-5p on the growth, invasion and migration of ccRCC cells and to verify the target genes of miR-181a-5p.

Results: As a differential miRNA of ccRCC, miR-181a-5p is significantly up-regulated in ccRCC patients and has a high diagnostic accuracy. High expression of miR-181a-5p is related to poor progress free interval (PFI). KIT, MECOM, COL4A6, EGF, and MAPK10 are the target genes of miR-181a-5p, which are significantly down-regulated in ccRCC patients and have high diagnostic accuracy. Low expression of these genes is associated with disease progression and poor prognosis of ccRCC. In addition, miR-181a-5p and its target genes were found to be associated with the immune infiltration of ccRCC. In vitro experiments proved that miR-181a-5p promote the growth, invasion and migration of ccRCC cells, and it was found that COL4A6, EGF, and MAPK10 are more likely to be the target genes of miR-181a-5p.

Conclusions: MiR-181a-5p may work together with its target genes to affect tumor-induced immune cell infiltration, and thus affect ccRCC. MiR-181a-5p and its target genes, such as EGF and MAPK10, may be novel prognostic markers and therapeutic targets for ccRCC patients.