KIAA1429 is a potential prognostic marker in colorectal cancer by promoting the proliferation via downregulating WEE1 expression in an m6A-independent manner.

Abstract

N6-methyladenosine (m6A), the most abundant mRNA modification in mammals, is involved in the metabolism of mRNA. KIAA1429 is regarded as the largest m6A methyltransferase and plays an important role in m6A modification. However, the prognostic value and function of KIAA1429 in colorectal cancer (CRC) are unclear. Quantitative real-time PCR and immunohistochemical assays were performed to evaluate the expression of KIAA1429 in CRC tissues. Kaplan-Meier survival curves and log-rank tests were used to assess the association between KIAA1429 expression and the prognosis of patients with CRC. CCK-8 assays, colony formation assays, cell cycle assays, and xenograft experiments were performed to investigate the effect of KIAA1429 on cell proliferation. RNA immunoprecipitation, methylated RNA immunoprecipitation assays, and RNA stability assays were conducted to explore the underlying mechanism. KIAA1429 was significantly upregulated in CRC tissues compared with adjacent normal tissues. Patients with higher expression of KIAA1429 had shorter overall survival than those with lower expression. Functionally, KIAA1429 promoted CRC cell proliferation in vitro and in vivo. Mechanistically, KIAA1429 negatively regulated the expression of WEE1 by decreasing its stability in an m6A-independent manner by binding to the third segment in the 3'-UTR of WEE1 mRNA. Moreover, butyrate decreased the expression of KIAA1429 by downregulating the level of the transcription factor NFκB1. Our findings indicated that KIAA1429 plays an oncogenic role in CRC cells by inhibiting the expression of WEE1 in an m6A-independent manner and is associated with poor survival in CRC patients. These results suggested that KIAA1429 might be a potential prognostic marker for CRC.