Abstract:
:Transforming growth factor-β (TGFβ) signaling acts as suppressor and inducer of tumor progression during the early and late stages of cancer, respectively. Some miRNAs have shown a regulatory effect on TGFβ signaling and here, we have used a combination of bioinformatics and experimental tools to show that hsa-miR-5590-3p is a regulator of multiple genes expression in the TGFβ signaling pathway. Consistent with the bioinformatics predictions, hsa-miR-5590-3p had a negative correlation of expression with TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 genes, detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Then, the dual luciferase assay supported the direct interaction between hsa-miR-5590-3p and TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4-3'UTR sequences. Consistently, the 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 the downregulation of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 expression in HCT-116 cells, detected by RT-qPCR, followed by cell cycle arrest in the 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 a negative regulator of the TGFβ/SMAD signaling pathway which acts through downregulation of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts. Therefore, it can be tested as a therapy target in cancers in which the TGFβ/SMAD pathway is deregulated.
journal_name
Biol Chemjournal_title
Biological chemistryauthors
Abedini Bakhshmand E,Soltani BMdoi
10.1515/hsz-2018-0264subject
Has Abstractpub_date
2019-04-24 00:00:00pages
677-685issue
5eissn
1431-6730issn
1437-4315pii
/j/bchm.just-accepted/hsz-2018-0264/hsz-2018-0264.journal_volume
400pub_type
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