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.

MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats by Targeting PRKAA2 Through the TGF-β1/Smad3 Signaling Pathway

“…The present study confirmed that PRKAA2 is a target gene of miR-27a and elevated miR-27a could down-regulate the expression of PRKAA2. A previous study indicated that miR-27a could inhibit MCF-7 cell growth by directly targeting the 3’-UTRs of PRKAA2 in breast cancer [41]. In addition, additional studies also revealed that PRKAA2 is involved in the susceptibility of diabetic nephropathy [42].…”

miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer

“…AMPK was also identified as a target by analysing miR-27a predictive tools (Supplementary Table 3) and in a different cell context. 37 We found that its expression increased in HCT116 and SW480 miR-27a_KD cells, as was its phosphorylation (p-AMPK Thr172), while both decreased in HT29 miR-27a_OE cells relative to controls (Fig. 4a).…”

MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy

“…We evaluated miRNA expression profiles from peripheral blood mononuclear cells (PBMCs) of the patients with active pulmonary TB, the lungs of Mtb strain H37Rv-infected C57/BL6 mice, and H37Rv-infected murine primary peritoneal macrophages. Using miRNA deep sequencing, we found that miR-27a, a microRNA mainly implicated in tumor cells 30 – 32 , was commonly upregulated in all samples compared to their representative controls (Fig. 1a–c ).…”

“…The possible antagonism of these two arms of responses underscore the importance to specifically target factors involved in the immune evasion strategies employed by Mtb . Other studies have reported that miR-27a targets various proteins that participate in different cellular functions including tumorigenesis, hypoxia, and ischemia 31 , 32 . Moreover, whether miR-27a may exert its function in the pathogenesis of TB through targeting other proteins warrants further clarification.…”