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BMP4-induced microRNAs in breast cancer cell lines

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BMP4-induced microRNAs in breast cancer cell lines

Background and aims: Breast cancer is the leading cause of mortality in women worldwide. In cancer, deregulation of signaling pathways, such as of the growth factor BMP4, is a common phenomenon. BMP4 is known to have a dualistic role in breast cancer, as it simultaneously decreases cell growth, but also increases migration and invasion. miRNAs are small regulators of several important cellular processes, and they have also been linked to cancer. Here, I wanted to study if microRNAs (miRNAs) partly affect these phenotypes.

Methods: The expression level of eight miRNAs after BMP4 treatment was studied in seven breast cancer cell lines and in one immortalized breast epithelial cell line using qRT-PCR. In the functional studies cell growth and migration were studied in two cell lines using proliferation assay and scratch assay, respectively. However, cell migration was studied only in MDA-MB-231 cells. For the proliferation assays, cells were treated with BMP4 and anti-miR inhibitors and the cells were counted at two time points, four and six or seven days after seeding. In the scratch assay a scratch was introduced to a confluent monolayer of cells and the closure area was measured at two hours’ intervals until the scratch closed up.

Results: Based on the qRT-PCR results two cell lines (BT-474 and MDA-MB-231) and two miRNAs (miR-16-5p and miR-106b-5p) were chosen for functional studies. In the functional studies it was seen that both of these miRNAs were upregulated after BMP4 treatment and the inhibition of these miRNAs increased cell growth. In addition, both miRNAs had a clear effect on cell migration. The inhibition of these miRNAs increased breast cancer cell migration further than the BMP4 treatment alone.

Conclusions: Both studied miRNAs, miR-16-5p and miR-106b-5p apparently cause part of the BMP4-induced reduction in breast cancer cell growth. On the other hand, it appears that high miR-16-5p and miR-106b-5p levels reduce the migration capability of MDA-MB-231 cells.

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