Статья

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

Lisa Svartdal NormannDepartment of Medical Genetics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayMiriam R. R. AureDepartment of Medical Genetics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwaySuvi‐Katri LeivonenApplied Tumor Genomics Research Program, Medical Faculty, University of Helsinki, Helsinki, FinlandMads H. HaugenDepartment of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayVesa HongistoVessela N. KristensenDepartment of Medical Genetics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayGunhild M. MælandsmoDepartment of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayKristine Kleivi SahlbergDepartment of Research and Innovation, Vestre Viken Hospital Trust, P.O. Box 800, 3004, Drammen, Norway. [email protected]

2021en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1038/s41598-021-90385-2

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar