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Background. miR-1251-5p was identified as a tumor suppressor in a variety of malignancies; however, its biological function in clear cell renal cell carcinoma (ccRCC) is unknown. Methods. The Cancer Genome Atlas (TCGA) database was used to download expression information, including miR-1251-5p, in 521 ccRCC tissues and 71 ordinary tissues, and bioinformatics was used to explore possible target mRNAs. The relationship between miR-1251-5p, target mRNA activity, and clinical factors was examined. To estimate the biological activity of miR-1251-5p and target mRNA in ccRCC cells, we used MTT, colony formation, enzyme-linked immunosorbent, and Transwell assays. We employed a dual-luciferase reporter assay and a western blot to examine the molecular mechanisms of miR-1251-5p in ccRCC cells. In addition, the expressions of miR-1251-5p and target mRNA were further verified in the GEO database. Results. Our findings revealed that miR-1251-5p binds with NPTX2’s 3′-UTR. In TCGA and GEO datasets, miR-1251-5p activity is found to be lower in ccRCC tissues than that in nearby conventional tissues, although NPTX2 activity is higher. In ccRCC sufferers, miR-1251-5p and NPTX2 act as biomarkers that indicate a bad prognosis. Meanwhile, in miR-1251-5p tissues, NPTX2 expression and multiple clinical variables (survival status, grade, T staging, N staging, M staging, and clinical stage) had significant differences  p &lt; 0.05 . Structurally, miR-1251-5p inhibited proliferation, migration, and immune escape of ccRCC cells by targeting NPTX2. Conclusion. Our findings indicate that miR-1251-5p constrained ccRCC cell advancement, migration, and immune evasion via targeting NPTX2, providing novel insights into ccRCC target treatment.

miR-1251-5p Overexpression Inhibits Proliferation, Migration, and Immune Escape in Clear Cell Renal Cell Carcinoma by Targeting NPTX2