Bibliographic Details
| Title: |
miR-204 suppresses cancer stemness and enhances osimertinib sensitivity in non-small cell lung cancer by targeting CD44 |
| Authors: |
Shang-Gin Wu, Tzu-Hua Chang, Meng-Feng Tsai, Yi-Nan Liu, Yen-Lin Huang, Chia-Lang Hsu, Han-Nian Jheng, Jin-Yuan Shih |
| Source: |
Molecular Therapy: Nucleic Acids, Vol 35, Iss 1, Pp 102091- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
MT: Noncoding RNAs, miR-204, CD44, osimertinib resistance, epidermal growth factor receptor, EGFR, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2162-2531 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2162253123003098; https://doaj.org/toc/2162-2531 |
| DOI: |
10.1016/j.omtn.2023.102091 |
| Access URL: |
https://doaj.org/article/0fe9a2a3fca74c738931950645a3cfe1 |
| Accession Number: |
edsdoj.0fe9a2a3fca74c738931950645a3cfe1 |
| Database: |
Directory of Open Access Journals |
