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N(6)-methyladenosine (m(6)A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer

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 expresse...

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Detalles Bibliográficos
Autores principales: Tang, Jun, Han, Tianci, Tong, Wei, Zhao, Jian, Wang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128911/
https://www.ncbi.nlm.nih.gov/pubmed/34001850
http://dx.doi.org/10.1038/s41420-021-00488-y
Descripción
Sumario: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.