miR-27a-mediated antiproliferative effects of metformin on the breast cancer cell line MCF-7.

Abstract

Metformin was demonstrated to have effects on breast cancer, and microRNA-27a (miR-27a) is a prognostic marker for breast cancer progression and patient survival. AMPKα2 was found to be a suppressor in breast cancer MCF-7 cells. Therefore, the present study aimed to explain this phenomenon in regards to the relationship between microRNAs (miRNAs) and their target genes and to predict how AMPKα2 may be a downstream target gene of miR-27a, thus exploring the new mechanism of metformin in the treatment of breast cancer regarding miRNAs. The MTT assay was used to assess whether metformin can inhibit the growth of breast cancer MCF-7 cells. The levels of miR-27a and AMPKα2 mRNA were examined using RT-PCR, and the expression levels of AMPKα2 and caspase-3 were determined by western blot analyses after MCF-7 cells were treated with metformin. The association of miR-27a and AMPKα2 was confirmed by transfecting cells with miR-27a mimics, miR-27a inhibitors and its negative control (NC), respectively. A luciferase assay was conducted to detect the miR-27a binding to the AMPKα2 3'-untranslated region (3'-UTR). The results of the MTT assay showed that metformin suppressed the growth of MCF-7 cells in a dose- and time‑dependent manner. miR-27a was downregulated, and AMPKa2 was upregulated after intervention with metformin, and caspase-3 was activated. Transfection tests showed that the expression of AMPKα2 was downregulated in the MCF-7 cells after transfection of the miR-27a mimics. The luciferase assay verified the binding of miR-27a to the AMPKα2 3'-UTR. In conclusion, metformin inhibited MCF-7 cell growth, and miR-27a plays a vital role in this process by targeting AMPKα2.

• Authors: Wei Zhao, Xiaohui Zhang, Jia Liu, Bei Sun, Hua Tang, Hong Zhang
• Journal: Oncology reports (Oncol Rep) Vol. 36 Issue 6 Pg. 3691-3699 (Dec 2016) ISSN: 1791-2431 [Electronic] Greece
• PMID: 27779715 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• Antimetabolites, Antineoplastic
• MIRN27 microRNA, human
• MicroRNAs
• Metformin
• PRKAA2 protein, human
• AMP-Activated Protein Kinases

Topics

• 3' Untranslated Regions
• AMP-Activated Protein Kinases (genetics, metabolism)
• Antimetabolites, Antineoplastic (pharmacology)
• Apoptosis
• Base Sequence
• Binding Sites
• Breast Neoplasms (drug therapy, enzymology, genetics)
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Humans
• MCF-7 Cells
• Metformin (pharmacology)
• MicroRNAs (physiology)
• RNA Interference