MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro

Abstract HER2-positive (HER2 +) breast cancer patients that do not respond to targeted treatment have a poor prognosis. The effects of targeted treatment on endogenous microRNA (miRNA) expression levels are unclear. We report that responsive HER2 + breast cancer cell lines had a higher number of miR...

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Autores principales:	Lisa Svartdal Normann, Miriam Ragle Aure, Suvi-Katri Leivonen, Mads Haugland Haugen, Vesa Hongisto, Vessela N. Kristensen, Gunhild Mari Mælandsmo, Kristine Kleivi Sahlberg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b40ee361d9441319955d2b6754721b1
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spelling	oai:doaj.org-article:0b40ee361d9441319955d2b6754721b12021-12-02T14:47:38ZMicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro10.1038/s41598-021-90385-22045-2322https://doaj.org/article/0b40ee361d9441319955d2b6754721b12021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90385-2https://doaj.org/toc/2045-2322Abstract HER2-positive (HER2 +) breast cancer patients that do not respond to targeted treatment have a poor prognosis. The effects of targeted treatment on endogenous microRNA (miRNA) expression levels are unclear. We report that responsive HER2 + breast cancer cell lines had a higher number of miRNAs with altered expression after treatment with trastuzumab and lapatinib compared to poorly responsive cell lines. To evaluate whether miRNAs can sensitize HER2 + cells to treatment, we performed a high-throughput screen of 1626 miRNA mimics and inhibitors in combination with trastuzumab and lapatinib in HER2 + breast cancer cells. We identified eight miRNA mimics sensitizing cells to targeted treatment, miR-101-5p, mir-518a-5p, miR-19b-2-5p, miR-1237-3p, miR-29a-3p, miR-29c-3p, miR-106a-5p, and miR-744-3p. A higher expression of miR-101-5p predicted better prognosis in patients with HER2 + breast cancer (OS: p = 0.039; BCSS: p = 0.012), supporting the tumor-suppressing role of this miRNA. In conclusion, we have identified miRNAs that sensitize HER2 + breast cancer cells to targeted therapy. This indicates the potential of combining targeted drugs with miRNAs to improve current treatments for HER2 + breast cancers.Lisa Svartdal NormannMiriam Ragle AureSuvi-Katri LeivonenMads Haugland HaugenVesa HongistoVessela N. KristensenGunhild Mari MælandsmoKristine Kleivi SahlbergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lisa Svartdal Normann Miriam Ragle Aure Suvi-Katri Leivonen Mads Haugland Haugen Vesa Hongisto Vessela N. Kristensen Gunhild Mari Mælandsmo Kristine Kleivi Sahlberg MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro
description	Abstract HER2-positive (HER2 +) breast cancer patients that do not respond to targeted treatment have a poor prognosis. The effects of targeted treatment on endogenous microRNA (miRNA) expression levels are unclear. We report that responsive HER2 + breast cancer cell lines had a higher number of miRNAs with altered expression after treatment with trastuzumab and lapatinib compared to poorly responsive cell lines. To evaluate whether miRNAs can sensitize HER2 + cells to treatment, we performed a high-throughput screen of 1626 miRNA mimics and inhibitors in combination with trastuzumab and lapatinib in HER2 + breast cancer cells. We identified eight miRNA mimics sensitizing cells to targeted treatment, miR-101-5p, mir-518a-5p, miR-19b-2-5p, miR-1237-3p, miR-29a-3p, miR-29c-3p, miR-106a-5p, and miR-744-3p. A higher expression of miR-101-5p predicted better prognosis in patients with HER2 + breast cancer (OS: p = 0.039; BCSS: p = 0.012), supporting the tumor-suppressing role of this miRNA. In conclusion, we have identified miRNAs that sensitize HER2 + breast cancer cells to targeted therapy. This indicates the potential of combining targeted drugs with miRNAs to improve current treatments for HER2 + breast cancers.
format	article
author	Lisa Svartdal Normann Miriam Ragle Aure Suvi-Katri Leivonen Mads Haugland Haugen Vesa Hongisto Vessela N. Kristensen Gunhild Mari Mælandsmo Kristine Kleivi Sahlberg
author_facet	Lisa Svartdal Normann Miriam Ragle Aure Suvi-Katri Leivonen Mads Haugland Haugen Vesa Hongisto Vessela N. Kristensen Gunhild Mari Mælandsmo Kristine Kleivi Sahlberg
author_sort	Lisa Svartdal Normann
title	MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro
title_short	MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro
title_full	MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro
title_fullStr	MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro
title_full_unstemmed	MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro
title_sort	microrna in combination with her2-targeting drugs reduces breast cancer cell viability in vitro
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0b40ee361d9441319955d2b6754721b1
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MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro

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