KIAA1429 acts as an oncogenic factor in breast cancer by regulating CDK1 in an N6-methyladenosine-independent manner

Most N6-methyladenosine (m(6)A) associated regulatory proteins (i.e., m(6)A writer, eraser, and reader proteins) are involved in the pathogenesis of various cancers, mostly in m(6)A-dependent manners. As a component in the m(6)A 'writers', KIAA1429 is reported to be an RNA-binding protein and involved in the m(6)A modification, mRNA splicing and processing. Till now, the functions of KIAA1429 in tumorigenesis and related mechanism have not been reported. In the present study, we found KIAA1429 was highly expressed in breast cancer tissues, but frequently down-regulated in non-cancerous breast tissues. The overall survival of breast cancer patients with high-expression KIAA1429 was significantly shorter than those with low-expression KIAA1429. Then, we demonstrated that KIAA1429 was associated with breast cancer proliferation and metastasis in vivo and in vitro. The potential targeting genes of KIAA1429 in breast cancer were identified by RNA immunoprecipitation sequencing. One of these genes is cyclin-dependent kinase 1 (CDK1), which plays an oncogenic role in cancers. Furthermore, we confirmed that KIAA1429 played its oncogenic role in breast cancer by regulating CDK1 by an m(6)A-independent manner. 5'-fluorouracil was found to be very effective in reducing the expression of KIAA1429 and CDK1 in breast cancer. These findings indicated that KIAA1429 could promote breast cancer progression and was correlated with pathogenesis. It may represent a promising therapeutic strategy on breast cancer, especially in combination with CDK1 treatment.