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MAML1 promotes ESCC aggressiveness through upregulation of EMT marker TWIST1

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Abstract

Background

Mastermind-like 1 (MAML1) is the main transcriptional co-activator of Notch signaling pathway. It plays essential roles in several pathways including MEF2C, p53, Nf-кB and Wnt/β-catenin. TWIST1 is known as a regulator of epithelial mesenchymal transition (EMT), which is considered as a primary step in promotion of tumor cell metastasis. Since concomitant expression of these genes was observed in tumors, our aim in this study was to elucidate the linkage between MAML1 and TWIST1 co-overexpression in esophageal squamous cell carcinoma (ESCC).

Results

While MAML1 silencing significantly down-regulated TWIST1, its ectopic expression up-regulated TWIST1 expression in both mRNA and protein levels in KYSE-30 cells. Expression of mesenchymal markers was increased significantly after MAML1 and TWIST1 ectopic expression, while epithelial markers expression was significantly decreased after silencing of both genes. Concomitant protein expression of MAML1 and TWIST1 was significantly observed in ESCC patients. Enforced expression of TWIST1 had no impact on MAML1 gene expression in KYSE-30 cells.

Conclusion

The results clearly suggest transcriptional regulation of TWIST1 by MAML1 transcription factor in ESCC cells KYSE-30. Since TWIST1 is known as an EMT inducing marker, our results may revealed the mastermind behind TWIST1 function and introduced MAML1 as an upstream master regulator of TWIST1 and EMT in KYSE-30 cells.

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Data availability

All raw data are available on case of request.

Abbreviations

MAML1:

Mastermind like 1

ESCC:

Epithelial squamous cell carcinoma

EMT:

Epithelial mesenchymal transition

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Funding

This study was funded by a Grant (No. 91001291) from Iran National Science Foundation (INSF).

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Authors and Affiliations

  1. Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran

    Mohammad Mahdi Forghanifard

  2. Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Shirin Azaraz, Sima Ardalan Khales & Dorsa Morshedi Rad

  3. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Reza Abbaszadegan

Authors
  1. Mohammad Mahdi Forghanifard
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  2. Shirin Azaraz
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  3. Sima Ardalan Khales
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  4. Dorsa Morshedi Rad
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  5. Mohammad Reza Abbaszadegan
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Contributions

MMF designed the study, analyzed data, drafted and edited the manuscript. ShA, SAKh, and DMR performed the experiments. MRA supervised the project and had a scientific revision on the manuscript.

Corresponding author

Correspondence to Mohammad Reza Abbaszadegan.

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The study was approved by ethics committee of Mashhad University of Medical Sciences and informed consent was obtained from all individual participants included in the study.

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The authors declare that they have no conflict of interest.

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Forghanifard, M.M., Azaraz, S., Ardalan Khales, S. et al. MAML1 promotes ESCC aggressiveness through upregulation of EMT marker TWIST1. Mol Biol Rep 47, 2659–2668 (2020). https://doi.org/10.1007/s11033-020-05356-z

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  • DOI: https://doi.org/10.1007/s11033-020-05356-z

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