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

  • Elham Abedini Bakhshmand und Bahram Mohammad Soltani EMAIL logo
Veröffentlicht/Copyright: 29. November 2018
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 400 Heft 5

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.

Keywords: breast cancer; dual luciferase assay; hsa-miR-5590-3p; SMAD; TGFβ signaling

Acknowledgments

The authors would like to thank 4402 lab mates TMU. This work has been supported by Tarbiat Modares University financial aids.

  1. Conflict of interest statement: The authors declare that there are no conflicts of interest with any financial organization regarding the material discussed in the manuscript.

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Received: 2018-05-27
Accepted: 2018-10-29
Published Online: 2018-11-29
Published in Print: 2019-05-27

©2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hsz-2018-0264
Schlagwörter für diesen Artikel
breast cancer; dual luciferase assay; hsa-miR-5590-3p; SMAD; TGFβ signaling

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Complexity of type IV collagens: from network assembly to function
  4. Structural and mechanistic aspects of S-S bonds in the thioredoxin-like family of proteins
  5. Oxidative stress and antioxidants in the pathophysiology of malignant melanoma
  6. Research Articles/Short Communications
  7. Genes and Nucleic Acids
  8. Dynamic characteristics of the mitochondrial genome in SCNT pigs
  9. Protein Structure and Function
  10. Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1
  11. Molecular Medicine
  12. The comparative biochemistry of viruses and humans: an evolutionary path towards autoimmunity
  13. MiR-23a-3p-regulated abnormal acetylation of FOXP3 induces regulatory T cell function defect in Graves’ disease
  14. Cell Biology and Signaling
  15. Evidence for a protective role of the CX3CL1/CX3CR1 axis in a model of amyotrophic lateral sclerosis
  16. LncRNA TINCR/microRNA-107/CD36 regulates cell proliferation and apoptosis in colorectal cancer via PPAR signaling pathway based on bioinformatics analysis
  17. Regulatory effect of hsa-miR-5590-3P on TGFβ signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts
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