The Role and Mechanism of KIAA1429‐Mediated m6A Modification in Pancreatic Adenocarcinoma

This study aimed to study the mechanism by which m6A methyltransferase, KIAA1429, affect pancreatic adenocarcinoma (PAAD) cell malignant behaviors in relation to N6-methyladenosine (m6A) modification. RT-qPCR, Western blot, immunohistochemistry (IHC), and m6A RNA immunoprecipitation (Me-RIP) assays were performed on PAAD tumor and adjacent non-tumor tissues (n = 39) to detect KIAA1429, AKT2 mRNA and protein levels, as well as overall tissue RNA m6A methylation levels. Tumor cells were transfected with siRNA targeting KIAA1429 (si-KIAA1429) or plasmids overexpressing AKT2 (oe-AKT2). Cell activities were assessed, followed by assessment of autophagic flux using the mRFP-GFP-LC3 reporter. In PAAD tissues and cell lines, KIAA1429 was substantially expressed. In PAAD patients, this expression was linked to a considerably lower overall and disease-specific survival rate. KIAA1429 knockdown inhibited PAAD cell malignant behaviors and promoted autophagy. Mechanistically, KIAA1429 mediated AKT2 m6A modification to enhance AKT2 mRNA stability and upregulate AKT2 expression, partially reversing the mediating effects of KIAA1429 knockdown on PAAD cell malignant behaviors and autophagy. KIAA1429 knockdown also inhibited PAAD tumor growth in vivo. KIAA1429 promotes PAAD cell malignant behaviors while inhibiting autophagy activity by mediating AKT2 m6A modification and enhancing AKT2 expression.