Regulatory effect of hsa-miR-5590-3P on TGF β signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts.

Regulatory effect of hsa-miR-5590-3P on TGFβ signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts. Biol Chem. 2018 Nov 01;: Authors: Bakhshmand EA, Soltani BM Abstract Transforming growth factor-β (TGFβ) signaling acts as suppressor and inducer of tumor progression during early and late stages of cancer, respectively. Some miRNAs have shown regulatory effect on TGFβ signaling and here, we have used combination of bioinformatics and experimental tools to show that hsa-miR-5590-3p is a regulator of multiple genes expression in TGFβ signaling pathway. Consistent to the bioinformatics predictions, hsa-miR- 5590-3p had a negative correlation of expression with TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 genes, detected by RT-qPCR. Then, dual luciferase assay supported direct interaction between hsa-miR-5590-3p and TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 -3'UTR sequences. Consistently, TGFβ-R1 protein level was reduced following the overexpression of hsa-miR-5590-3p, detected by Western analysis. Also, hsa-miR-5590-3p overexpression brought about downregulation of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 expression in HCT-116 cells, detected by RT-qPCR, followed by cell cycle arrest in sub-G1 phase, detected by flow cytometry. RT-qPCR results indicated that hsa-miR-5590-3p is significantly downregulated in breast tumor tissues (late stage) compared to their normal pairs. Altogether, data introduces hsa-miR-5590-3p as negativ...
Source: Biological Chemistry - Category: Chemistry Tags: Biol Chem Source Type: research