# miR-4429 inhibits ccRCC proliferation, migration, and invasion by directly targeting CD274

## TL;DR

This study shows that miR-4429 reduces kidney cancer growth and spread by targeting CD274 and affecting a key signaling pathway.

## Contribution

miR-4429 is newly identified as a tumor suppressor in ccRCC by directly targeting CD274 and modulating PI3K/AKT signaling.

## Key findings

- miR-4429 is down-regulated in ccRCC tissues and inhibits cancer cell proliferation, migration, and invasion.
- CD274 is a direct target of miR-4429 and is up-regulated in ccRCC tissues.
- miR-4429 regulates the PI3K/AKT signaling pathway, offering a potential therapeutic target for ccRCC.

## Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive urological malignancies and a highly immunogenic cancer. Yet, its pathogenesis is still not fully understood. This study analyzed the role of the miR-320 family in ccRCC using bioinformatics algorithms and a series of in vitro experiments. miR-4429 was found to be significantly down-regulated in ccRCC tissues and cell lines, while overexpression of miR-4429 significantly inhibited renal cancer cell proliferation, migration, and invasion in vitro. In addition, the UALCAN database, immunohistochemistry, and protein blotting results showed that CD274 expression was up-regulated in ccRCC tissues and correlated with higher histologic grading. Dual luciferase assay indicated that CD274 was a direct target of miR-4429. Overexpression of miR-4429 in 786-O, Caki-2 cells significantly inhibited CD274 expression. KEGG results indicated that the potential target function of miR-4429 was associated with the PI3K/AKT signaling pathway, and protein blotting verified the results. In summary, this data shows that miR-4429 targets CD274 and inhibits ccRCC proliferation, migration, and invasion by regulating PI3K/AKT signaling, thus potentially providing a promising therapeutic target and prognostic biomarker for renal cell carcinoma patients.

The online version contains supplementary material available at 10.1007/s12672-024-01055-4.