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

Permanent lenke
https://hdl.handle.net/10037/21579
DOI
https://doi.org/10.1038/s41598-021-90385-2
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Åpne
article.pdf (2.001Mb)
Publisert versjon (PDF)
Dato
2021-05-25
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Svartdal, Lisa Gregusson; Aure, Miriam Ragle; Leivonen, Suvi-Katri; Haugen, Mads Haugland; Hongisto, Vesa; Kristensen, Vessela N.; Mælandsmo, Gunhild Mari; Sahlberg, Kristine Kleivi
Sammendrag
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.
Forlag
Springer
Sitering
Svartdal, Aure, Leivonen, Haugen, Hongisto, Kristensen, Mælandsmo, Sahlberg. MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro. Scientific Reports. 2021;11
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Copyright 2021 The Author(s)

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