N6-methyladenosine (m6A) writer KIAA1429 accelerates gastric cancer oxaliplatin chemoresistance by targeting FOXM1.

Abstract

Chemical modification plays a critical role in regulating human cancer progression, especially N6-methyladenosine (m6A). However, m6A writer KIAA1429-mediated m6A modification in gastric cancer (GC) tumorigenesis remains largely unknown. The levels of mRNA and protein were detected using RT-qPCR and western blot. Thehalf maximal inhibitory concentration (IC50)of oxaliplatin (OXA) resistance isdetected using CCK-8 assay. The binding within moleculars was identified using RIP-PCR. Results found that KIAA1429 was upregulated in GC tissue samples and its high expression acted as a prognostic factor of poor survival in patients with GC. Functional assays indicated that KIAA1429 promoted the proliferation of GC cells, besides, KIAA1429 accelerated the half maximal inhibitory concentration (IC50) of oxaliplatin (OXA) resistance. Mechanistically, online prediction found that there was possible m6A modification site on FOXM1 mRNA. KIAA1429 could target the m6A modification site on FOXM1. Notably, KIAA1429 facilitated the GC OXA resistance in GC cells by promoting FOXM1 mRNA stability. Taken together, our study reveals the functions and mechanism for KIAA1429 and exposes KIAA1429 as a key player in GC chemoresistance.