The oncogenic effect and mechanism of LINC00520/miR-372/SLC7A11 axis in renal clear cell carcinoma

To investigate the expression, function, and potential mechanism of long non-coding RNA LINC00520 as a competitive endogenous RNA in clear cell renal cell carcinoma (ccRCC) by regulating the miR-372/SLC7A11 axis in renal cell carcinoma progression. The expression profiles of LINC00520 and SLC7A11 in various cancers were analyzed using the TCGA database. Using renal cell carcinoma cell lines, the interactions between LINC00520, miR-372, and SLC7A11 were validated through qRT-PCR, Western blot, RNA immunoprecipitation (RIP), and dual-luciferase reporter assays. The effects of LINC00520 on the cell cycle, apoptosis, migration, invasion, and proliferation of renal cancer cells were evaluated using techniques such as flow cytometry, Transwell assay, and immunofluorescence staining. The involvement of miR-372 was validated through functional rescue experiments. Result: LINC00520 and SLC7A11 showed high expression in various cancers (including ccRCC), and their expression levels in ccRCC were positively correlated with tumor staging and grading. Mechanistically, LINC00520 acts as a ceRNA by directly binding to miR-372, relieving its inhibition of the target gene SLC7A11 and upregulating its expression. Functionally, overexpression of LINC00520 can promote the cell cycle progression, migration, invasion, proliferation, and inhibit apoptosis of renal cancer cells, which can be partially reversed by miR-372 mimetics. On the contrary, knocking down LINC00520 produces the opposite phenotype, and this effect can be partially rescued by miR-372 inhibitors. In addition, LINC00520 can downregulate the expression of the tumor suppressor gene P53. LINC00520 plays a pro-cancer role in renal cell carcinoma by adsorbing miR-372 through ceRNA, thereby releasing the inhibition of SLC7A11 by miR-372 and ultimately promoting tumor malignant progression. The LINC00520/miR-372/SLC7A11 axis is a potential prognostic biomarker and therapeutic target for renal cell carcinoma.