KIAA1429 promotes clear cell renal cell carcinoma progression by regulating MYC mRNA stability
Xu Zhu, Cheng Shen, Yong Zhang, Xinfeng Chen, Wei Zhang, Bing Zheng, Zhan Chen
TL;DR
KIAA1429 promotes kidney cancer by stabilizing MYC mRNA, and targeting this interaction could be a new treatment strategy.
Contribution
KIAA1429 is identified as a novel m6A-dependent regulator of MYC mRNA stability in clear cell renal cell carcinoma.
Findings
KIAA1429 depletion inhibits tumor growth, proliferation, migration, and invasion in ccRCC.
KIAA1429 binds to MYC mRNA and enhances its stability through m6A methylation.
The KIAA1429-MYC axis is proposed as a promising therapeutic target in ccRCC.
Abstract
KIAA1429, a core component of the m6A methyltransferase complex, is upregulated in clear cell renal cell carcinoma (ccRCC) and is associated with poor survival rates. Functional assays and in vivo models demonstrate that genetic depletion of KIAA1429 markedly inhibits tumor growth, as well as cancer cell proliferation, migration, and invasion. Mechanistically, KIAA1429 directly binds to the 3′ untranslated region (3′ UTR) of MYC mRNA and catalyzes site-specific m6A methylation, thereby enhancing transcript stability and augmenting MYC protein expression. Collectively, these findings identify KIAA1429 as a critical m6A-dependent post-transcriptional regulator of MYC and nominate the KIAA1429-MYC regulatory axis as a promising therapeutic target in ccRCC. •KIAA1429 is upregulated in clear cell renal cell carcinoma and indicates poor prognosis•Silencing KIAA1429 suppresses tumor growth,…
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Taxonomy
TopicsFerroptosis and cancer prognosis · RNA Research and Splicing · PI3K/AKT/mTOR signaling in cancer