MicroRNA-130a-3p regulates osimertinib resistance by targeting runt-related transcription factor 3 in lung adenocarcinoma

Shintani, Takuya; Shun, Yu Ting; Toyozumi, Yuji; Ikemura, Kenji; Shiroyama, Takayuki; Nagatomo, Izumi; Jingushi, Kentaro; Takeda, Yoshito; Kumanogoh, Atsushi; Okuda, Masahiro

doi:https://doi.org/10.1038/s41598-024-76196-1

MicroRNA-130a-3p regulates osimertinib resistance by targeting runt-related transcription factor 3 in lung adenocarcinoma

Shintani, Takuya; Shun, Yu Ting; Toyozumi, Yuji et al.

Scientific Reports, 2024, 14, 24429

Number of Access:1,317（2025-07-18 09:50 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98340

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Title	MicroRNA-130a-3p regulates osimertinib resistance by targeting runt-related transcription factor 3 in lung adenocarcinoma
Creator	NRID 1000040762076 1000040762076 CreatorName Shintani, Takuya
	CreatorName Shun, Yu Ting
	CreatorName Toyozumi, Yuji
	NRID 1000070513935 1000070513935 ORCID 0000-0003-1870-9571 0000-0003-1870-9571 researchmap permalink Kenji_Ikemura Kenji_Ikemura Scopus Author ID 36783115100 36783115100 CreatorName Ikemura, Kenji
	NRID 1000060860062 1000060860062 researchmap permalink shiroyama_t shiroyama_t Scopus Author ID 36476578400 36476578400 CreatorName Shiroyama, Takayuki
	NRID 1000010570583 1000010570583 researchmap permalink saxon-w saxon-w Scopus Author ID 13404305500 13404305500 CreatorName Nagatomo, Izumi
	NRID 1000080707571 1000080707571 ORCID 0000-0002-2274-4962 0000-0002-2274-4962 researchmap permalink _kj _kj Scopus Author ID 13807151700 13807151700 CreatorName Jingushi, Kentaro
	NRID 1000040452388 1000040452388 researchmap permalink yoshi10 yoshi10 Scopus Author ID 7404001848 7404001848 CreatorName Takeda, Yoshito
	NRID 1000010294125 1000010294125 researchmap permalink read0051725 read0051725 Scopus Author ID 6602726311 6602726311 ORCID 0000-0003-4749-7117 0000-0003-4749-7117 CreatorName Kumanogoh, Atsushi
	NRID 1000070252426 1000070252426 researchmap permalink read0042639 read0042639 Scopus Author ID 56856467300 56856467300 CreatorName Okuda, Masahiro
Subject	Extracellular vesicles
	Lung adenocarcinoma
	MicroRNA-130a-3p
	Osimertinib resistance
	Runt-related transcription factor 3
Description	Shintani T., Shun Y.T., Toyozumi Y., et al. MicroRNA-130a-3p regulates osimertinib resistance by targeting runt-related transcription factor 3 in lung adenocarcinoma. Scientific Reports 14, 24429 (2024); https://doi.org/10.1038/s41598-024-76196-1.
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.
Publisher	Nature Research
Source Title	Scientific Reports
Volume (Issue)	14
Page	24429
Date of Issued	2024-10-18
Language	English
Handle URL	https://hdl.handle.net/11094/98340
eISSN	20452322
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41598-024-76196-1
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Scientific Reports. 2024, 14, p. 24429
DC.title	MicroRNA-130a-3p regulates osimertinib resistance by targeting runt-related transcription factor 3 in lung adenocarcinoma
DC.creator	Shintani, Takuya
	Shun, Yu Ting
	Toyozumi, Yuji
	Ikemura, Kenji
	Shiroyama, Takayuki
	Nagatomo, Izumi
	Jingushi, Kentaro
	Takeda, Yoshito
	Kumanogoh, Atsushi
	Okuda, Masahiro
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-10-18
DC.identifier	https://doi.org/10.1038/s41598-024-76196-1
DC.subject	Extracellular vesicles
	Lung adenocarcinoma
	MicroRNA-130a-3p
	Osimertinib resistance
	Runt-related transcription factor 3
DC.description	Shintani T., Shun Y.T., Toyozumi Y., et al. MicroRNA-130a-3p regulates osimertinib resistance by targeting runt-related transcription factor 3 in lung adenocarcinoma. Scientific Reports 14, 24429 (2024); https://doi.org/10.1038/s41598-024-76196-1.
DCTERMS.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.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	98340
citation_title	MicroRNA-130a-3p regulates osimertinib resistance by targeting runt-related transcription factor 3 in lung adenocarcinoma
citation_author	Shintani, Takuya
	Shun, Yu Ting
	Toyozumi, Yuji
	Ikemura, Kenji
	Shiroyama, Takayuki
	Nagatomo, Izumi
	Jingushi, Kentaro
	Takeda, Yoshito
	Kumanogoh, Atsushi
	Okuda, Masahiro
citation_publisher	Nature Research
citation_language	English
citation_date	2024-10-18
citation_journal_title	Scientific Reports
citation_volume	14
citation_firstpage	24429
citation_doi	https://doi.org/10.1038/s41598-024-76196-1
citation_public_url	https://hdl.handle.net/11094/98340

MicroRNA-130a-3p regulates osimertinib resistance by targeting runt-related transcription factor 3 in lung adenocarcinoma

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