Hsa-miR-587 Regulates TGFβ/SMAD Signaling and Promotes Cell Cycle Progression (Pages: 158-164)

Mahnaz Jahangirimoez , Abdallah Medlej , Mahmoud Tavallaie , Bahram Soltani *,


TGFβ/SMAD signaling pathway plays important roles in various biological processes. It acts as a tumor suppressor during the early stages of cancer progression. Discovering the regulators of this pathway provides important options for therapeutic strategies. Here, we searched for candidate miRNAs that potentially target the important components of the TGFβ signaling pathway.


In the current experimental study, we first used a set of bioinformatics software to predict miRNAs that target TGFβ components. After that, RT-qPCR was used to detect the expression of miR-587, TGFBR2, SMAD4, p21, CCND1 and C-MYC genes in the transfected HEK293T and HCT116 cells. Dual Luciferase assay was performed to analyze miRNA and target genes’ interactions. Propidium Iodide flow cytometry was used to determine the cell cycle progression in HEK293T and HCT116 cells under hsa-miR-587 (miR-587) overexpression circumstances.


Multiple miRNA responsive elements (MREs) were predicted for miR-587 within the 3’UTRs of the TGFBR2 and SMAD4 genes. Overexpression of miR-587 in HEK293T and HCT116 cells resulted in the downregulation of TGFBR2 and SMAD4 genes. In addition, TGFβ/SMAD signaling downstream target gene, P21, was significantly downregulated in the HCT116 cells overexpressing miR-587. After that, dual luciferase assay analysis provided evidence about a direct interaction between miR-587 and the 3’UTR sequences of TGFBR2 and SMAD4 genes. Moreover, miR-587 overexpression in HEK293T and HCT116 cells resulted in reducing the SubG1 cell populations in both cell lines, detected by flow cytometry.


Altogether, our data revealed an important role of miR-587 in regulating TGFβ/SMAD signaling, and promoting cell cycle progression. These characteristics suggest miR-587 as an important candidate for further cancer therapy research.