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

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.

Automated summary

HER2-positive breast cancer patients that do not respond to targeted treatment have a poor prognosis. Through a high-throughput screen, it was found that certain miRNA mimics can sensitize HER2+ breast cancer cells to targeted therapy, with miR-101-5p showing a correlation with better prognosis in patients. This suggests the potential of combining targeted drugs with miRNAs to improve current treatments for HER2+ breast cancers.