| RRC ID |
83584
|
| 著者 |
Shintani T, Shun YT, Toyozumi Y, Ikemura K, Shiroyama T, Nagatomo I, Jingushi K, Takeda Y, Kumanogoh A, Okuda M.
|
| タイトル |
MicroRNA-130a-3p regulates osimertinib resistance by targeting runt-related transcription factor 3 in lung adenocarcinoma.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Overcoming resistance to epidermal growth factor receptor tyrosine kinase inhibitors, including osimertinib, is urgent to improve lung cancer treatment outcomes. Extracellular vesicle (EV)-derived microRNAs (EV-miRNAs) play important roles in drug resistance and serve as promising biomarkers. In this study, we aimed to identify EV-miRNAs associated with osimertinib resistance and investigate their clinical relevance. The release of excess EVs was confirmed in the osimertinib-resistant lung adenocarcinoma cell line PC9OR. The exposure of PC9OR-derived EVs and EV-miRNAs to PC9 cells increased cell viability after osimertinib treatment. Microarray analysis revealed that miR-130a-3p was upregulated in EVs derived from PC9OR cells and another osimertinib-resistant cell line (H1975OR). Transfection with miR-130a-3p attenuated osimertinib-induced cytotoxicity and apoptosis in both PC9 and H1975 cells, whereas osimertinib resistance in PC9OR cells was reversed after miR-130a-3p inhibition. Bioinformatics analysis revealed that runt-related transcription factor 3 is a target gene of miR-130a-3p, and it induced osimertinib resistance in PC9 cells. Patients with lower baseline serum miR-130a-3p concentrations had longer progression-free survival. miR-130a-3p is a potential therapeutic target and a predictive biomarker of osimertinib resistance in adenocarcinomas.
|
| 巻・号 |
14(1)
|
| ページ |
24429
|
| 公開日 |
2024-10-18
|
| DOI |
10.1038/s41598-024-76196-1
|
| PII |
10.1038/s41598-024-76196-1
|
| PMID |
39424918
|
| PMC |
PMC11489462
|
| MeSH |
Acrylamides* / pharmacology
Acrylamides* / therapeutic use
Adenocarcinoma of Lung* / drug therapy
Adenocarcinoma of Lung* / genetics
Adenocarcinoma of Lung* / metabolism
Adenocarcinoma of Lung* / pathology
Aged
Aniline Compounds* / pharmacology
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Apoptosis / drug effects
Cell Line, Tumor
Drug Resistance, Neoplasm* / genetics
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
Indoles
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Lung Neoplasms* / metabolism
Lung Neoplasms* / pathology
Male
MicroRNAs* / genetics
MicroRNAs* / metabolism
Middle Aged
Pyrimidines
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
PC-9(RCB4455) |
