KIAA1429 Induces the Tumorigenesis of Clear Cell Renal Cell Carcinoma via Regulating the N6-Methyladenosine Modification of Thymosin Beta-10.

Abstract

N⁶-Methyladenosine (m⁶A) is a reversible RNA modification that regulates tumorigenesis. KIAA1429, a critical component of the m⁶A methyltransferase complex, has an unclear role in clear cell renal cell carcinoma (ccRCC). Here, we investigated the role of KIAA1429 in ccRCC tumorigenesis. The expressions of KIAA1429 and thymosin beta-10 (TMSB10) in ccRCC samples were evaluated using quantitative real-time PCR (qRT-PCR). The malignant features of ccRCC cells were assessed via CCK-8, colony formation, transwell migration, and invasion assays, as well as in vivo tumor xenograft models. The relationship between KIAA1429 and TMSB10 was verified via Pearson correlation analysis, methylated RNA immunoprecipitation, qRT-PCR, and Western blotting assays. Functional rescue experiments further confirmed their interaction. We found that KIAA1429 was highly expressed in ccRCC, and its silencing significantly suppressed cell proliferation, migration, invasion, and tumor growth in vivo, while overexpression had the opposite effect. Bioinformatics and mechanistic analyses identified TMSB10 as a downstream target of KIAA1429, whose expression was upregulated in an m⁶A-dependent manner. Furthermore, overexpressing TMSB10 partially reversed the inhibitory effects of KIAA1429 silencing on ccRCC cells. Moreover, TMSB10 overexpression partially reversed the inhibitory effects of KIAA1429 knockdown. Taken together, our findings demonstrate that KIAA1429 promotes ccRCC tumorigenesis by enhancing TMSB10 expression via m⁶A modification, suggesting it as a potential prognostic biomarker and therapeutic target. However, the lack of clinical validation limits the immediate translational impact of these findings.