mir-451a-5p Modulates Breast Cancer Cell Apoptosis, Migration, and Chemosensitivity to Carboplatin through the PTEN Pathway

Abstract

Background: MicroRNAs (miRNAs) can play essential roles in the modulation of cancer cell growth, survival, and resistance to chemotherapy. Thus, we hypothesized that restoration of miR-451a-5p (a tumor suppressor) might affect sensitivity to chemotherapeutics in breast cancer cells. Methods: For this purpose, malignant breast cancer cells (MDA-MB-231) were transfected with miR-451a-5p mimic and exposed with carboplatin. Then, the apoptotic rate was evaluated by flow cytometry and DAPI staining (apoptosis), q-RT-PCR (expression levels of caspase-3, caspase-8, MMP9, ROCK, vimentin, c-Myc genes). Moreover, the proliferation and migration of cancer cells were assessed by MTT (cell viability) and wound healing assay. The western blot assay was used for protein expression of PTEN, AKT, and P-AKT. Results: Our findings demonstrated that a combination of miR-451a-5p restoration with carboplatin administration could additionally induce apoptosis, repress the proliferation and migration, and also increase PTEN protein expression with no significant alteration on the AKT/P-AKT protein expressions in the breast cancer cells. The present data was analyzed using GraphPad Prism 6 software by non-parametric one-way ANOVA and t-test. Conclusion: In conclusion, it seems that overexpression of miR-451a can enhance the chemosensitivity of breast cancer cells to carboplatin therapy. Thus, it may shed new light on miR-451a management of breast cancer chemoresistance and may be a beneficial strategy for future cancer therapy. However, further studies, particularly in other signaling pathways, should be required.

Keywords

• apoptosis
• breast cancer
• carboplatin
• chemoresistance
• mir-451a-5p