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ARID1A regulates E-cadherin expression in colorectal cancer cells: a promising candidate therapeutic target

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Abstract

Background

Metastasis is a major cause of death in Colorectal cancer (CRC) patients, and the Epithelial–mesenchymal transition (EMT) has been known to be a crucial event in cancer metastasis. Downregulated expression of AT-rich interaction domain-containing protein 1A (ARID1A), a bona fide tumor suppressor gene, plays an important role in promoting EMT and CRC metastasis, but the underlying molecular mechanisms remain poorly understood. Here, we evaluated the impact of ARID1A knockdown and overexpression on the expression of EMT‑related genes, E-cadherin and β-catenin, in human CRC cells.

Methods and results

The expression levels of ARID1A, E-cadherin and β-catenin in CRC cell lines were detected via real-time quantitative PCR (qPCR) and western blot. ARID1A overexpression and shRNA-mediated knockdown were performed to indicate the effect of ARID1A expression on E-cadherin and β-catenin expression in CRC cell lines. The effect of ARID1A knockdown on the migration ability of HCT116 cells was assessed using wound-healing assay. We found that the mRNA and protein expression of adhesive protein E-cadherin was remarkably downregulated in response to shRNA-mediated ARID1A knockdown in HCT116 and HT29 cells. Conversely, overexpression of ARID1A in SW48 cells significantly increased E-cadherin expression. In addition, ARID1A silencing promoted the migration of HCT116 cells. ARID1A knockdown and overexpression did not alter the level of β-catenin expression.

Conclusions

Our study demonstrates that E-cadherin levels were closely correlated with ARID1A expression. Thus, ARID1A downregulation may promote CRC metastasis through decreasing EMT‑related protein E-cadherin and promoting epithelial cell movement. ARID1A could represent a promising candidate therapeutic target for CRC.

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Data availability

All data are included in this article and datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to express their sincere gratitude to Shiraz University of Medical Sciences for financially supporting the study (No. 17288).

Funding

This work was supported by the Shiraz University of Medical Sciences [Grant number: 17288].

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Shiraz University of Medical Sciences, P.O. Box: 1167, Shiraz, Iran

    Mehran Erfani, Zohreh Mostafavi-Pour, Sayed Mohammad Shafiee & Pooneh Mokarram

  2. Department of Biochemistry, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

    Mehran Erfani

  3. Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mozhdeh Zamani & Pooneh Mokarram

  4. Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Younes Hosseini

  5. Department of Hematology, School of Paramedical, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammadreza Saeidnia

Authors
  1. Mehran Erfani
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  2. Mozhdeh Zamani
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  3. Seyed Younes Hosseini
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  4. Zohreh Mostafavi-Pour
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  5. Sayed Mohammad Shafiee
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  6. Mohammadreza Saeidnia
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  7. Pooneh Mokarram
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Contributions

PM and ME contributed to the study conception and design. Material preparation, data collection and analysis were performed by ME, MZ, SYH, ZM and SMS. The first draft of the manuscript was written by ME and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Pooneh Mokarram.

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Conflict of interest

The authors declared that they have no conflict of interest.

Ethical approval

Ethics approval was obtained from the Ethics Committee of Shiraz University of Medical Sciences prior to this study (IR.SUMS.REC.1398.1390).

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Erfani, M., Zamani, M., Hosseini, S.Y. et al. ARID1A regulates E-cadherin expression in colorectal cancer cells: a promising candidate therapeutic target. Mol Biol Rep 48, 6749–6756 (2021). https://doi.org/10.1007/s11033-021-06671-9

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  • DOI: https://doi.org/10.1007/s11033-021-06671-9

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