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The interaction between MALAT1 target, miR-143-3p, and RALGAPA2 is affected by functional SNP rs3827693 in breast cancer

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Abstract

A higher expression of MALAT1 has been reported in breast cancer. However, more studies are needed to decipher the mechanisms by which this lncRNA imposes its oncogenic effects. In this study, blood and tissue samples were taken from healthy normal and breast cancer subjects. qPCR was used to analyze the gene expression. HRM-PCR method was carried out to genotype the selected samples. Computational analysis was recruited to find novel targets of MALAT1 and miR-143-3p. The data analyses revealed that MALAT1 was up-regulated in breast cancer and could be a distinctive factor to diagnose cancer. The expression of MALAT1 was inversely correlated with miR-143-3p expression in the studied clinical samples. The down-regulation of miR-143-3p was proven in the clinical tumor samples as compared to the healthy controls. A negative correlation of miR-143-3p with its putative target, RALGAPA2 was observed. A functional SNP rs3827693 located within the 3′UTR region of RALGAPA2 mRNA was validated in this study to associate with breast cancer risk. The rs3827693 allele G significantly decreased the breast cancer incidence and augmented the negative correlation between RALGAPA2 and miR-143-3p, presumably through strengthening the interaction between these two transcripts. This study proposed MALAT1 miR-143-3p and miR-143-3p RALGAPA2 axis in breast cancer, whereby the latter can be altered by the clinically functional SNP rs3827693.

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Acknowledgements

We would like to greatly appreciate the donors of blood and tissue donors of this study.

Funding

This research was financially supported by Zist-fanavari Novin Biotechnology Institute, Isfahan, Iran.

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Author notes

  1. Nasrin Fattahi Dolatabadi, Arezo Dehghani, Elham Shahand and Mohammadreza Yazdanshenas equally contributed to this work.

Authors and Affiliations

  1. Zist-Fanavari Novin Biotechnology Institute, Isfahan, Iran

    Nasrin Fattahi Dolatabadi, Arezo Dehghani, Elham Shahand, Mohammadreza Yazdanshenas, Atefe Zamani & Mansoureh Azadeh

  2. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran

    Hossein Tabatabaeian & Kamran Ghaedi

  3. Anahid Breast Cancer Clinic, Isfahan Healthcare City, Isfahan, Iran

    Hossein Tabatabaeian

  4. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

    Kamran Ghaedi

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  1. Nasrin Fattahi Dolatabadi
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  2. Arezo Dehghani
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  5. Hossein Tabatabaeian
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Correspondence to Hossein Tabatabaeian or Kamran Ghaedi.

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All procedures performed in this study involving human participants were in accordance with the ethical standards of the Ethics Committee of Isfahan University of Medical Sciences (approval number: 3838988), regarding 64th World Medical Association General Assembly of Helsinki declaration amended in October 2013..

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Fattahi Dolatabadi, N., Dehghani, A., Shahand, E. et al. The interaction between MALAT1 target, miR-143-3p, and RALGAPA2 is affected by functional SNP rs3827693 in breast cancer. Human Cell 33, 1229–1239 (2020). https://doi.org/10.1007/s13577-020-00422-x

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