pmid: 31721529,   nlmid 101566618,  doi:10.22074/cellj.2020.6483

Hsa-miR-587 Regulates TGF?/SMAD Signaling and Promotes Cell Cycle Progression.


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

Vol. 22, Issue 22, Jul.2020

Cell journal (Cell J),  ISSN 2228-5806

Abstract

Transforming growth factor beta/single mothers against decapentaplegic (TGF?/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 microRNAs (miRNAs) that potentially target the critical components of the TGF? signaling pathway. In the current experimental study, we first predicted miRNAs that target TGF? components using a bioinformatics software. After that, quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-587, TGFBR2, SMAD4, p21, CCND1 and c-MYC genes in transfected HEK293T and HCT116 cells. Dual Luciferase assay was performed to analyze the interactions between miRNAs and the target genes. Propidium iodide flow cytometry was used to determine 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 downregulation of TGFBR2 and SMAD4 genes. In addition, a downstream target gene of TGF?/SMAD signaling, P21, was significantly downregulated in the HCT116 cells overexpressing miR-587. Dual luciferase assay analysis provided evidence that there is 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, as detected by flow cytometry. Altogether, our data revealed an important role for miR-587 in regulating TGF?/SMAD signaling and promoting cell cycle progression. These characteristics suggest that miR-587 is an important candidate for cancer therapy research.


MESH Headings


Article Keywords

Cancer | Cell Cycle | TGF?/SMAD Signaling | miR-587 |


Chemical

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