https://scholars.lib.ntu.edu.tw/handle/123456789/639916
標題: | miR-204 suppresses cancer stemness and enhances osimertinib sensitivity in non-small cell lung cancer by targeting CD44 | 作者: | SHANG-GIN WU Chang, Tzu-Hua Tsai, Meng-Feng Liu, Yi-Nan YEN-LIN HUANG Hsu, Chia-Lang Jheng, Han-Nian JIN-YUAN SHIH |
關鍵字: | CD44; EGFR; EMT; MT: Noncoding RNAs; TKI; epidermal growth factor receptor; epithelial-to-mesenchymal transition; miR-204; osimertinib resistance; stemness; tyrosine kinase inhibitor | 公開日期: | 12-三月-2024 | 卷: | 35 | 期: | 1 | 來源出版物: | Molecular therapy. Nucleic acids | 摘要: | Osimertinib is an effective treatment option for patients with advanced non-small cell lung cancer (NSCLC) with EGFR activation or T790M resistance mutations; however, acquired resistance to osimertinib can still develop. This study explored novel miRNA-mRNA regulatory mechanisms that contribute to osimertinib resistance in lung cancer. We found that miR-204 expression in osimertinib-resistant lung cancer cells was markedly reduced compared to that in osimertinib-sensitive parental cells. miR-204 expression levels in cancer cells isolated from treatment-naive pleural effusions were significantly higher than those in cells with acquired resistance to osimertinib. miR-204 enhanced the sensitivity of lung cancer cells to osimertinib and suppressed spheroid formation, migration, and invasion of lung cancer cells. Increased miR-204 expression in osimertinib-resistant cells reversed resistance to osimertinib and enhanced osimertinib-induced apoptosis by upregulating BIM expression levels and activating caspases. Restoration of CD44 (the direct downstream target gene of miR-204) expression reversed the effects of miR-204 on osimertinib sensitivity, recovered cancer stem cell and mesenchymal markers, and suppressed E-cadherin expression. The study demonstrates that miR-204 reduced cancer stemness and epithelial-to-mesenchymal transition, thus overcoming osimertinib resistance in lung cancer by inhibiting the CD44 signaling pathway. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/639916 | ISSN: | 2162-2531 | DOI: | 10.1016/j.omtn.2023.102091 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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