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Introduction of miR-3613-3p as a regulator of transforming growth factor-β (TGF-β) signaling pathway in colorectal cancer

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Abstract

Introduction

Colorectal cancer (CRC) is the second common cancer and the fourth major reason of cancer death worldwide. Dysregulation of intracellular pathways, such as TGF-β/SMAD signaling, contributes to CRC development. MicroRNAs (miRNAs) are post-transcriptional regulators that are involved in CRC pathogenesis. Here, we aimed to investigate the effect of miR-3613-3p on the TGF-β /SMAD signaling pathway in CRC.

Methods & results

Bioinformatics analysis suggested that miR-3613-3p is a regulator of TGF-Β signaling downstream genes. Then, miR-3613-3p overexpression was followed by downregulation of TGF-βR1, TGF-βR2, and SMAD2 expression levels, detected by RT-qPCR. Additionally, dual luciferase assay supported the direct interaction of miR-3613-3p with 3’UTR sequences of TGF-βR1 and TGF-βR2 genes. Furthermore, reduced SMAD3 protein level following the miR-3613-3p overexpression verified its suppressive effect against TGF-β signaling in HCT-116 cells, detected by western blot analysis. Finally, miR-3613-3p overexpression induced sub-G1 arrest in HCT116 cells, detected by flow cytometry, and promoted downregulation of cyclin D1 protein expression, which was detected by western blotting analysis.

Conclusion

Our findings indicated that miR-3613-3p plays an important role in CRC by targeting the TGF-β/SMAD signaling pathway and could be considered as a new candidate for further therapy investigations.

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Data availability

All of the related data including originals of the experiments will be available upon request.

Abbreviations

CRC:

Colorectal cancer

WNT:

Wingless/Integrated

MAPK:

Mitogen-Activated Protein Kinase

TGF-β:

Transforming Growth Factor Beta

TGF-βR:

Transforming Growth Factor Beta Receptor

SMAD:

Small mothers against decapentaplegic

R-SMAD:

Receptor-regulated Smad

CO-SMAD:

Common mediator Smad

SMAD6/7:

Inhibitory Smad 6/7

miRNAs:

MicroRNAs

MREs:

miRNA recognition elements

3’UTR:

3’ Untranslated Region

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Acknowledgements

We thank 4402 Lab mates for their cooperation’s.

Funding

This work was supported by Tarbiat Modares University, National Science Foundation (INSF# 96012116) financial aids.

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Author notes

  1. Monireh Jafarian and Tabasom Hasannia contributed equally to this work.

Authors and Affiliations

  1. Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Monireh Jafarian, Tabasom Hasannia, Parisa Badameh, Mehrdad Behmanesh & Bahram M. Soltani

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  1. Monireh Jafarian
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  2. Tabasom Hasannia
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  3. Parisa Badameh
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  4. Mehrdad Behmanesh
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  5. Bahram M. Soltani
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Contributions

MJ & TH; performed the experiments, TH & PB; Helped the experiments BMS; designed and supervised the experiments, MB; advised the research.

Corresponding author

Correspondence to Bahram M. Soltani.

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Conflict of interest

The authors declare that there are no conflicts of interest with any financial organization regarding the material discussed in the manuscript. Also, none of the authors have any non-financial conflict of interest.

Ethical approval

This study was carried out in accordance with the recommendations of the Research Ethics Committee of Tarbiat Modares University. All subjects gave written informed consent in accordance with the Declaration of Helsinki. Permission from the responsible authorities was granted. (Ethical code: IR.MODARES.REC.1400.136)

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The authors declare no competing interests.

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Jafarian, M., Hasannia, T., Badameh, P. et al. Introduction of miR-3613-3p as a regulator of transforming growth factor-β (TGF-β) signaling pathway in colorectal cancer. Mol Biol Rep 51, 728 (2024). https://doi.org/10.1007/s11033-024-09419-3

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