N6-methyladenosine (m6A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer
Tang Jun, Tianci Han, Wei Tong, Jian Zhao, Wei Wang
Abstract
Abstract N 6 -methyladenosine (m 6 A) modification has been convincingly identified to be a critical regulator in human cancer. However, the contribution of m 6 A to NSCLC gefitinib resistance is still largely unknown. Here, we screened and identified that m 6 A methyltransferase KIAA1429 was highly expressed in gefitinib-resistant NSCLC cells (PC9-GR), tissues, and closely related to unfavorable survival. Functionally, KIAA1429 accelerated the gefitinib resistance of NSCLC in vitro. Depletion of KIAA1429 repressed the tumor growth of PC9-GR cells in vivo. Mechanistically, KIAA1429 enhanced the mRNA stability of HOXA1 through targeting its 3′-untranslated regions (3′-UTR). Overall, our findings indicate that KIAA1429 plays essential oncogenic roles in NSCLC gefitinib resistance, which may provide a feasible therapeutic target for NSCLC.