Scientific Reports (May 2021)

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

  • Lisa Svartdal Normann,
  • Miriam Ragle Aure,
  • Suvi-Katri Leivonen,
  • Mads Haugland Haugen,
  • Vesa Hongisto,
  • Vessela N. Kristensen,
  • Gunhild Mari Mælandsmo,
  • Kristine Kleivi Sahlberg

DOI
https://doi.org/10.1038/s41598-021-90385-2
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 11

Abstract

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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.