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MicroRNA expression is deregulated by aberrant methylation in B-cell acute lymphoblastic leukemia mouse model

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Abstract

Background

The expression of microRNAs (miRNAs) in the serum of B-cell acute lymphoblastic leukemia (B-ALL) patients is abnormal. Nevertheless, the underlying mechanism remains unclear. Recent studies indicate that the methylation state of circulating cell-free DNA (cfDNA) is different between cancer patients and healthy individuals. Therefore, we speculate that abnormal expression of miRNA may be associated with cfDNA methylation.

Methods

A green fluorescent protein (GFP) labeled B-ALL transplantation animal model was established to explore the relationship between the miRNA expression and cfDNA methylation of the related gene. Quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of miRNAs. Further, cfDNA methylation levels of the related genes were evaluated through bisulfite sequencing polymerase chain reaction (BSP).

Results

The expression levels of miR-196b, miR-203, miR-34a-5p, miR-335-3p, miR-34b-5p, miR-615, miR-375-3p and miR-193b-5p in the serum of the model mice were significantly lower than those of the control group (P < 0.05). The methylation level of miR-196b promoter in cfDNA of the model group was significantly lower than that of the control group (P < 0.05), whereas no significant difference was noted in miR-203 promoter. The methylation levels of miR-196b and miR-203 coding region in cfDNA of the model group were significantly higher than those of the control group (P < 0.05).

Conclusions

These results showed that CpG island hypermethylation in the miRNA coding region of cfDNA is related to the low expression of miR-196b and miR-203.

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Data availability

All data generated or analyzed during this study are included in this article.

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Acknowledgements

This study was supported by National Science Funding of China (Grant No. 81201354), Science and Technology Development Program of Jilin Province (Grant No. 20200403118SF), Suzhou Institute of Biomedical Engineering and Technology (SIBET) of the Chinese Academy of Sciences-Jilin Science and Technology Cooperation Project (Grant No. E055PY03) and Beihua University Graduate Innovation Program (Grant No. 2019-062).

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Author notes

  1. Wei Xia and Limei Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of Experiment Center, School of Medical Technology, Beihua University, No.3999 Binjiang East Road, Fengman District, Jilin City, Jilin Province, China

    Yidan Wang, Yihan Wang, Hetong Hui, Xinyuan Fan, Tianqi Wang, Wei Xia & Limei Liu

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  1. Yidan Wang
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by YDW, YHW, HTH, XYF and TQW. The manuscript was written by YDW and reviewed by LML and WX. All authors read and approved the final manuscript.

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Correspondence to Wei Xia or Limei Liu.

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This manuscript does not report studies involving human participants. The use of animals and sample collection procedures were in accordance with the ethical standards. Approval was obtained from the Institutional Animal Care and Use Committee of Beihua University.

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Wang, Y., Wang, Y., Hui, H. et al. MicroRNA expression is deregulated by aberrant methylation in B-cell acute lymphoblastic leukemia mouse model. Mol Biol Rep 49, 1731–1739 (2022). https://doi.org/10.1007/s11033-021-06982-x

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