The m6 RNA methylation regulator KIAA1429 is associated with autophagy-mediated drug resistance in lung cancer.

Abstract

N6-methyladenosine (m6A) modification plays a crucial role in cancer progression. However, the role of m6A modification-mediated autophagy underlying non-small cell lung cancer (NSCLC) gefitinib resistance remains unknown. Here, we discovered that m6A methyltransferase KIAA1429 was highly expressed in NSCLC gefitinib-resistant cells (PC9-GR) as well as tissues, and KIAA1429 high expression was associated with poor survival. In addition, silent KIAA1429 repressed gefitinib resistance in NSCLC and reduced tumor growth invivo. Mechanistically, KIAA1429 stabilized WTAP, a significant player in autophagy, by binding to the 3' untranslated regions (3'-UTR) of WTAP. In a word, our findings indicated that KIAA1429 could elevate NSCLC gefitinib resistance, which may provide a promising targeted therapy for NSCLC patients.