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The Effect of miR-155 on DNA Damage in Mesenchymal Stem Cells

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Abstract

Considering the crucial role of miR-155 in DNA repair regulation, the aim of this study was to evaluate the effect of miR-155 on the expression of DNA repair factors involved in single- and double-strand DNA breaks (SSBs and DSBs) and mismatch repair (MMR) in mesenchymal stem cells (MSCs). MSCs were isolated from the bone marrow of a healthy individual, and then confirmed by their adipogenic/osteogenic differentiation and flow cytometric analysis of surface markers of MSCs (CD105, CD90, and CD73). MSCs transfection by green fluorescent protein (GFP) plasmid bearing miR-155 was verified by fluorescent microscope, and was measured via analyzing the percentage of transfected cells compared to non-transfected by flow cytometry. The expression of miR-155 and mRNAs related to DNA repair response system, i.e. XRCC1, XRCC5, XRCC6, and RAD51, were assessed by real-time PCR. Overexpression of miR-155 in MSCs was significant compared to control (p = 0.034). Increase in the expression of DNA repair genes, including XRCC1, XRCC6, XRCC5, and RAD51 was not significant (p = 0.066, 0.108, 0.092, 0.631, and 0.262, respectively). In conclusion, although the expression of DNA repair genes by miR-155 overexpression was not significant, it has the potential to affect DNA repair genes expression.

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REFERENCES

  1. Chang, S., Wang, R.-H., Akagi, K., Kim, K.-A., Martin, B.K., Cavallone, L., Haines, D. C., Basik, M., Mai, P., and Poggi, E. J. N., Isaaks, C., Looli, L.M., Mun, K.S., Greene, M.H., Byers, S.W., Teo, S.H., Deng, C.X., Sharan, S.K., Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155, Nature Med., 2011, vol. 17, pp. 1275–1282.

    Article  CAS  Google Scholar 

  2. Cruet-Hennequart, S., Prendergast, A., Barry, F., and Carty, M., Human mesenchymal stem cells (hMSCs) as targets of DNA damaging agents in cancer therapy, Curr Cancer Drug Targets, 2010, vol. 10, pp. 411–421.

    Article  CAS  Google Scholar 

  3. Czochor, J. R., Sulkowski, P., and Glazer, P. M., miR-155 overexpression promotes genomic instability by reducing high-fidelity polymerase delta expression and activating error-prone DSB repair, Mol. Cancer Res., 2016, vol. 14, pp. 363–373.

    Article  CAS  Google Scholar 

  4. Dang, Y., Wang, X., Hao, Y., Zhang, X., Zhao, S., Ma, J., Qin, Y., and Chen, Z.-J., MicroRNA-379-5p is associated with biochemical premature ovarian insufficiency through PARP1 and XRCC6, Cell Death Dis., 2018, vol. 9, p. 106.

    Article  Google Scholar 

  5. De Castro Marcondes, J.P., Floriano, J.F., Reyes, D.A., Quiroz, S.B., Hallur, L.S., Barbosa, A.M., and Rudge, M.V., DNA Damage levels and DNA repair capability of bone marrow-derived mesenchymal stem cells from Sprague Dawley® SPF rats as a quality parameter before surgical transfection for the treatment of gestational diabetic myopathy, FASEB J, 2019, vol. 33, no. 1 (suppl.), abstract no. 662.20.

  6. Gasparini, P., Lovat, F., Fassan, M., Casadei, L., Cascione, L., Jacob, N. K., Carasi, S., Palmieri, D., Costinean, S., and Shapiro, C.L., Huebner, K., and Croce, C.M., Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation, Proc. Natl. Acad. Sci. U. S. A., 2014, vol. 111, pp. 4536–4541.

    Article  CAS  Google Scholar 

  7. Gui, Z., Zhang, H., Tan, Q., Ling, X., Liu, Z., Peng, J., Shao, J., Wu, M., Yuan, Q., and Li, J., Poly (ADP-ribose) polymerase-1 promotes expression of miR-155 by the up-regulation of methyl-CpG binding domain protein 2 in TK6 cells exposed to hydroquinone, Toxicol. In Vitro, 2019, vol. 55, pp. 51–57.

    Article  CAS  Google Scholar 

  8. He, M., Zhou, W., Li, C., and Guo, M., MicroRNAs, DNA damage response, and cancer treatment, Int. J. Mol., 2016, vol. 17, pp. 2087.

    Article  Google Scholar 

  9. Kuo, Y.-C., Li, Y.-S. J., Zhou, J., Shih, Y.-R. V., Miller, M., Broide, D., Lee, O. K.-S., and Chien, S., Human mesenchymal stem cells suppress the stretch–induced inflammatory miR-155 and cytokines in bronchial epithelial cells, PLoS One, 2013, vol. 8. e71342.

    Article  CAS  Google Scholar 

  10. Liu, H., Zhong, L., Yuan, T., Chen, S., Zhou, Y., An, L., Guo, Y., Fan, M., Li, Y., and Sun, Y., MicroRNA-155 inhibits the osteogenic differentiation of mesenchymal stem cells induced by BMP9 via downregulation of BMP signaling pathway, Int. J. Mol. Med., 2018, vol. 41, pp. 3379–3393.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Lu, Y., Song, S., Jiang, X., Meng, Q., Wang, C., Li, X., Yang, Y., Xin, X., Zheng, Q., and Wang, L., miR675 accelerates malignant transformation of mesenchymal stem cells by blocking DNA mismatch repair, Mol. Ther. Nucleic Acids, 2019, vol. 14, pp. 171–183.

    Article  CAS  Google Scholar 

  12. Luo, H., Liang, H., Chen, Y., Chen, S., Xu, Y., Xu, L., Liu, J., Zhou, K., Peng, J., and Guo, G., miR-7-5p overexpression suppresses cell proliferation and promotes apoptosis through inhibiting the ability of DNA damage repair of PARP-1 and BRCA1 in TK6 cells exposed to hydroquinone, Chem. Biol. Interact., 2018, vol. 283, pp. 84–90.

    Article  CAS  Google Scholar 

  13. Michaille, J.J., Awad, H., Fortman, E.C., Efanov, A.A., and Tili, E., miR-155 expression in antitumor immunity: the higher the better?, Genes Chromosomes Cancer, 2019, vol. 58, pp. 208–218.

    Article  CAS  Google Scholar 

  14. Morales, J., Li, L., Fattah, F.J., Dong, Y., Bey, E.A., Patel, M., Gao, J., and Boothman, D. A., Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases, Crit. Rev. Eukaryot. Gene Expr., 2014, vol. 24, pp.

  15. Nariman-Saleh-Fam, Z., Saadatian, Z., Daraei, A., Mansoori, Y., Bastami, M., and Tavakkoli-Bazzaz, J., The intricate role of miR-155 in carcinogenesis: potential implications for esophageal cancer research, Biomark. Med., 2019, vol. 13, pp. 147–159.

    Article  CAS  Google Scholar 

  16. Poh, W., Dilley, R.L., Moliterno, A.R., Maciejewski, J. ., Pratz, K.W., McDevitt, M.A., and Herman, J.G.J.C.C.R., BRCA1 promoter methylation is linked to defective homologous recombination repair and elevated miR-155 to disrupt myeloid differentiation in myeloid malignancies, Clin. Cancer Res., 2019, vol. 25, pp. 2513–2522.

    Article  CAS  Google Scholar 

  17. Ren, F., Su, H., Jiang, H., and Chen, Y., Overexpression of miR-623 suppresses progression of hepatocellular carcinoma via regulating the PI3K/Akt signaling pathway by targeting XRCC5, J. Cell Biochem., 2019, vol. 121, pp. 213–223.

    Article  Google Scholar 

  18. Rong, S., and Zhang, J., Modulatory role of microRNA-124 in targeting Ku70 during post-stroke neuronal apoptosis, Int. J. Clin. Exp. Pathol., 2017, vol. 10, pp. 3697–3702.

    CAS  Google Scholar 

  19. Tang, L., Peng, Y.-z., Li, C.-g., Jiang, H.-W., Mei, H., and Hu, Y., Prognostic and clinicopathological significance of miR-155 in hematologic malignancies: a systematic review and meta-analysis, J. Cancer, 2019, vol. 10, p. 654.

    Article  CAS  Google Scholar 

  20. Wang, Y., and Taniguchi, T. J. C. c., MicroRNAs and DNA damage response: implications for cancer therapy, Cell Cycle, 2013, vol. 12, pp. 32–42.

    Article  CAS  Google Scholar 

  21. Wang, Y., Yang, L., Liu, X., Hong, T., Wang, T., Dong, A., Li, J., Xu, X., and Cao, L., miR-431 inhibits adipogenic differentiation of human bone marrow-derived mesenchymal stem cells via targeting insulin receptor substance 2, Stem Cell Res. Ther., 2018, vol. 9, p. 231.

    Article  CAS  Google Scholar 

  22. Xia, M., Zhang, Q., Luo, M., Li, P., Wang, Y., Lei, Q., and Guo, A.-Y., Regulatory network analysis reveals the oncogenesis roles of feed-forward loops and therapeutic target in T-cell acute lymphoblastic leukemia, BMC Med Genomics, 2019, vol. 12, p. 8.

    Article  Google Scholar 

  23. Xu, C., Ren, G., Cao, G., Chen, Q., Shou, P., Zheng, C., Du, L., Han, X., Jiang, M., and Yang, Q., miR-155 regulates immune modulatory properties of mesenchymal stem cells by targeting TAK1-binding protein 2, J. Biol. Chem., 2013, vol. 288, pp. 11074–11079.

    Article  CAS  Google Scholar 

  24. Yu, J., Shi, J., Zhang, Y., Zhang, Y., Huang, Y., Chen, Z., and Yang, J., The replicative senescent mesenchymal stem/stromal cells defect in DNA damage response and anti-oxidative capacity, Int. J. Med. Sci., 2018, vol. 15, p. 771.

    Article  CAS  Google Scholar 

  25. Zeng, H., Hu, M., Lu, Y., Zhang, Z., Xu, Y., Wang, S., Chen, M., Shen, M., Wang, C., and Chen, F.J.T.F.J., microRNA 34a promotes ionizing radiation–induced DNA damage repair in murine hematopoietic stem cells, FASEB J., 2019, vol., pp. fj. 201802639R.

  26. Zhao, M.-J., Xie, J., Shu, W.-J., Wang, H.-Y., Bi, J., Jiang, W., and Du, H.-N., MiR-15b and miR-322 inhibit SETD3 expression to repress muscle cell differentiation, Cell Death Dis., 2019, vol. 10, p. 183.

    Article  Google Scholar 

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ACKNOWLEDGMENTS

This work was financially supported by grant IR. IUMS. REC1396.30774 from the vice chancellor for research affairs of School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.

Funding

This work received research funding (grant IR. IUMS. REC1396.30774) from School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran. The terms of this arrangement have been reviewed and approved by the Iran University of Medical Sciences in accordance with its policy on objectivity in research.

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Correspondence to Minoo Shahidi.

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COMPLIANCE WITH ETHICAL STANDARDS

Conflict of interest. The authors declare that they have no conflict of interest.Statement of compliance with standards of research involving humans as subjects. Bone morrow aspiration of a healthy person was performed after the approval from of the Tarbiat Modares University ethics committee (Number: 2344017).

AUTHOR CONTRIBUTIONS

M.Sh. as a director of the project has conceived the manuscript and revised it. M.Sh. wrote the manuscript. M.A.Gh. and M.Sh. performed the technical tests.

Additional information

Abbreviarions: BER—base excision repair, BM—bone marrow, DDR—DNA damage response, DSBs—double-strand breaks, HCC—hepatocellular carcinoma, HSCs—hematopoietic stem cells, miR—microRNAs, MMR—mismatch repair, MSCs— mesenchymal stem cells, NER—nucleotide excision repair, NHEJ—non-homologous end joining, SSBs – single-strand breaks.

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Mohammad Shokouhian, Shahidi, M. & Gholampour, M.A. The Effect of miR-155 on DNA Damage in Mesenchymal Stem Cells. Cell Tiss. Biol. 14, 341–348 (2020). https://doi.org/10.1134/S1990519X20050077

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  • DOI: https://doi.org/10.1134/S1990519X20050077

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