Paclitaxel May Inhibit Epithelial-Mesenchymal Transition Properties of Triple-negative Breast Cancer Cell Line via Altering the Expression of EMT-promoting and –inhibiting MicroRNAs

Background: Abnormal expressions of microRNAs are related to various cancers such as breast cancer for which paclitaxel is widely used as a chemotherapeutic agent. We aimed to investigate the effect of paclitaxel treatment on the expression level of miR-۱۹۹a-۵p and miR-۱۰b, involved in epithelial-mesenchymal transition (EMT) process in breast cancer cell lines. Methods: Human breast cancer cell lines BT-۴۷۴, SKBR-۳, MDA-MB-۲۳۱, and MCF-۷ were cultured and MTT assay was used to determine IC۵۰ of paclitaxel. RNA was extracted, cDNA was synthesized, and the expression level of miRNAs and genes was quantitatively determined using real-time PCR. Results: After treatment with paclitaxel, the expression level of miR-۱۹۹a-۵p significantly decreased in MCF-۷ and SKBR-۳ cell lines, while it increased in MDA-MB-۲۳۱ and BT-۴۷۴. The expression level of miR-۱۰b was also significantly reduced in MCF-۷, MDA-MB-۲۳۱, and SKBR-۳ and increased in BT-۴۷۴ cell lines following treatment with paclitaxel. Our results further indicated that paclitaxel reduced the expression level of vimentin and MMP-۹ in MDA-MB-۲۳۱ cell line. Conclusion: Our findings revealed the increased expression of EMT-inhibitor miR-۱۹۹a-۵p and the decreased expression of metastamir miR-۱۰b after treatment of MDA-MB-۲۳۱ metastatic breast cancer cell line. Reduced expressions of vimentin and MMP-۹ were also observed, corroborating the inhibition of metastasis markers in this type of breast cancer. The therapeutic effect of paclitaxel may in part be due to the change in the balance of EMT-promoting and EMT-inhibiting miRNAs.

Keywords:

Breast cancer , MiR-۱۹۹a-۵p , MiR-۱۰b , Paclitaxel , Vimentin , MMP-۹