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 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.

miR-101-5p Acts as a Tumor Suppressor in HER2-Positive Breast Cancer Cells and Improves Targeted Therapy

“…We have previously shown that overexpression of miR-101-5p reduces cell viability measured by CellTiter-Glo assay in HER2+ KPL4 breast cancer cells alone and in combination with lapatinib and trastuzumab. 20 These data were confirmed here using a complementary cell proliferation assay measuring the confluence over time after miR-101-5p overexpression. Indeed, miR-101-5p overexpression inhibited proliferation compared to the scrambled negative control (Student’s t -test, p < 0.001; Figure 2A ).…”

“… 25 Previously, we have shown that miR-101-5p decrease cell viability in HER2+ breast cancer cells and sensitize the cells to targeted treatment. 20 The aim of the current study was to gain knowledge of the mechanisms involved in treatment response, by studying the effects on the proteomic landscape when combining miR-101-5p overexpression with HER2-targeting drugs.…”

“…We have previously shown the promising effects of combining miR-101-5p overexpression with trastuzumab and lapatinib to inhibit cell viability in HER2+ breast cancer cells that respond poorly to targeted treatment. 20 A high-throughput miRNA screen revealed miR-101-5p as one of eight promising miRNAs with sensitizing properties in HER2+ breast cancer cells. In the current study, we aim to investigate the molecular mechanisms that cause the sensitizing effect of miR-101-5p by studying changes in the proteomic landscape in HER2 cancer cells upon treatment.…”

Inflammatory Breast Cancer: The Secretome of HCMV+ Tumor-Associated Macrophages Enhances Proliferation, Invasion, Colony Formation, and Expression of Cancer Stem Cell Markers

“…After that, 20 mL (5 g/L) of MTT (3-(4,5dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) reagent was added to the designated wells. After a 4 h incubation, the MTT formazan precipitate was dissolved in dimethylsulphoxide (DMSO) (150 mL/well, Sigma-Aldrich, St. Louis, MO, USA) in a shaker for 5 min before reading the absorbance at 570 nm using a 96-well plate reader (Bio-Rad, Winooski, VT USA) (47)(48)(49).…”

MicroRNA-138-1-3p sensitizes sorafenib to hepatocellular carcinoma by targeting PAK5 mediated β-catenin/ABCB1 signaling pathway

“…1A). Evidences showed that miR-NAs own great potentials in combination cancer therapy [29][30][31]. For example, targeting miR-21 could enhance conventional chemotherapeutic efficacy, together with overcoming drug resistance and cancer recurrence [32].…”