Tang Jun, Han Tianci, Tong Wei, Zhao Jian, Wang Wei
No. 1 Department of Tuberculosis, Chest Hospital, Shenyang, Liaoning Province, 110044, China.
Department of Thoracic Surgery, Cancer Hospital of China Medical University, Shenyang, Liaoning Province, 110042, China.
Cell Death Discov. 2021 May 17;7(1):108. doi: 10.1038/s41420-021-00488-y.
N-methyladenosine (mA) modification has been convincingly identified to be a critical regulator in human cancer. However, the contribution of mA to NSCLC gefitinib resistance is still largely unknown. Here, we screened and identified that mA 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.
N-甲基腺苷（mA）修饰已被确凿地认定为人类癌症中的关键调节因子。然而，mA对非小细胞肺癌吉非替尼耐药性的作用仍 largely未知。在此，我们筛选并鉴定出mA甲基转移酶KIAA1429在吉非替尼耐药的非小细胞肺癌细胞（PC9-GR）、组织中高表达，且与不良生存密切相关。在功能上，KIAA1429在体外加速了非小细胞肺癌对吉非替尼的耐药性。敲低KIAA1429可在体内抑制PC9-GR细胞的肿瘤生长。机制上，KIAA1429通过靶向HOXA1的3'非翻译区（3'-UTR）增强其mRNA稳定性。总体而言，我们的研究结果表明KIAA1429在非小细胞肺癌吉非替尼耐药中起重要致癌作用，这可能为非小细胞肺癌提供一个可行的治疗靶点。
