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ABCC6P1 pseudogene induces ABCC6 upregulation and multidrug resistance in breast cancer

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Abstract

Background

The elevated drug efflux by ABC transports has been considered the primary mechanism of drug resistance in cancer. Recently, non-coding RNAs, such as pseudogenes, have been proposed to be involved in transporter-mediated drug resistance in cancer. The human genome has 22 ABC transporter pseudogenes. Among these pseudogenes, ABCC6P1 has co-expression with its ancestral gene in various human tissues. In the present study, we assessed the effect of ABCC6P1 pseudogene overexpression on ABCC6 expression and drug resistance.

Methods and results

The ABCC6P1 was transfected into the MCF-7 and MDA-MB-231 cells. In ABCC6P1-overexpressing cells, the ABCC6 level significantly increased. The results of cell treatment with doxorubicin, 5-fluorouracil, cisplatin, and paclitaxel showed that the survival of ABCC6P1-overexpressing cells was higher than normal cells. Furthermore, uptake of doxorubicin was lower in ABCC6P1-overexpressing cells.

Conclusions

In conclusion, our results show that overexpression of ABCC6P1 pseudogene induces the drug resistance phenotype, possibly through activation of the ancestral gene.

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Acknowledgements

The authors would like to thank Dr. Saeed Mohammadi for his helpful technical advice.

Funding

This work was financially supported by Golestan University of Medical Sciences (Grant Number 110477).

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Authors and Affiliations

  1. Department of Human Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran

    Mahnaz Hashemi & Masoud Golalipour

  2. Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran

    Masoud Golalipour

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  1. Mahnaz Hashemi
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  2. Masoud Golalipour
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Correspondence to Masoud Golalipour.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Research Ethics Committee at Golestan University of Medical Science (Ethics Number: IR.GOUMS.REC.1398.166).

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Hashemi, M., Golalipour, M. ABCC6P1 pseudogene induces ABCC6 upregulation and multidrug resistance in breast cancer. Mol Biol Rep 49, 9633–9639 (2022). https://doi.org/10.1007/s11033-022-07872-6

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