Skip to main content

Advertisement

SpringerLink
Log in

Investigation of XPD, miR-145 and miR-770 expression in patients with end-stage renal disease

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

The effective maintenance of genome integrity and fidelity is vital for the normal function of our tissues and organs, and the prevention of diseases. DNA repair pathways maintain genome stability, and the adequacy of genes acting in these pathways is essential for disease suppression and direct treatment responses. Chronic kidney disease is characterized by high levels of genomic damage. In this study, we examined the expression levels of the xeroderma pigmentosum group D (XPD) gene, which plays a role in the nucleotide excision repair (NER) repair mechanism, and the expression levels of miR-145 and miR-770 genes, which play a role in the regulation of the expression of the XPD gene, in hemodialysis patients with (n = 42) and without malignancy (n = 9) in pre- and post-dialysis conditions. We also evaluated these values with the clinical findings of the patients.

Methods & Results

Gene expression analysis was performed by real-time polymerase chain reaction (qRT-PCR). Compared to the individuals with normal kidney function (2.06 ± 0.32), the XPD gene expression was lower in the pre-dialysis condition both in hemodialysis patients without cancer (1.24 ± 0.18; p = 0.02) and in hemodialysis patients with cancer (0.82 ± 0.114; p = 0.001). On the other hand, we found that miR-145 and miR-770 expression levels were high in both groups. We also found that expression levels were affected by dialysis processes. A statistically significant positive correlation was found between miR-145 and mir770 expression levels in the pre-dialysis group of patients with (r=-0.988. p = 0.0001) and without (r=-0.934. p = 0.0001) malignancy.

Conclusions

Studies on DNA damage repair in the kidney will help develop strategies to protect kidney function against kidney diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data Availability

The data of the study are available upon request from the corresponding author.

References

  1. Obrador GT, Schultheiss UT, Kretzler M, Langham RG, Nangaku M, Pecoits-Filho R, Pollock C, Rossert J, Correa-Rotter R, Stenvinkel P, Walker R, Yang CW, Fox CS, Köttgen A (2011) Genetic and environmental risk factors for chronic kidney disease. Kidney Int Suppl 2017:88–106. https://doi.org/10.1016/j.kisu.2017.07.004

    Article  Google Scholar 

  2. Rangel-López A, Paniagua-Medina ME, Urbán-Reyes M, Cortes-Arredondo M, Alvarez-Aguilar C, López-Meza J, Ochoa-Zarzosa A, Lindholm B, García-López E, Paniagua JR (2013) Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study. Mutagenesis 28: 219 – 25. https://doi.org/10.1093/mutage/ges075

  3. Guven GS, Altiparmak MR, Trabulus S, Yalin AS, Batar B, Tunckale A, Guven M (2013) Relationship between genomic damage and clinical features in dialysis patients. Genet Test Mol Biomarkers 17:202–206. https://doi.org/10.1089/gtmb.2012.0301

    Article  CAS  PubMed  Google Scholar 

  4. Schupp N, Stopper H, Heidland (2016) DNA damage in chronic kidney disease: Evaluation of clinical biomarkers. Oxid Med Cell Longev 2016: 3592042. https://doi.org/10.1155/2016/3592042

  5. Luciani A, Denley MCS, Govers LP, Sorrentino V, Froese DS (2021) Mitochondrial DNA mutations in renal disease: an overview. Cell Mol Life Sci 78:6851–6867. https://doi.org/10.1007/s00018-021-03934-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Shirazian S, Starakiewicz P, Latcha S (2021) Cancer Screening in end-stage kidney disease. Adv Chronic Kidney Dis 28:502–508e1. https://doi.org/10.1053/j.ackd.2021.09.006

    Article  PubMed  Google Scholar 

  7. Vamvakas S, Bahner U, Heidlan A (1998) Cancer in end-stage renal disease: potential factors involved. Am J Nephrol 18:89–95. https://doi.org/10.1159/000013314

    Article  CAS  PubMed  Google Scholar 

  8. Hayashi K, Hishikawa A, Itoh H (2019) DNA damage repair and DNA methylation in the kidney. Am J Nephrol 50:81–91. https://doi.org/10.1159/000501356

    Article  CAS  PubMed  Google Scholar 

  9. Schmid U, Stopper H, Schweda F, Queisser N, Schupp N (2008) Angiotensin II induces DNA damage in the kidney. Cancer Res 68:9239–9246. https://doi.org/10.1158/0008-5472.CAN-08-1310

    Article  CAS  PubMed  Google Scholar 

  10. Duan M, Speer RM, Ulibarri J, Liu KJ, Mao P (2021) Transcription-coupled nucleotide excision repair: new insights revealed by genomic approaches. DNA Repair (Amst) 103:103126. https://doi.org/10.1016/j.dnarep.2021.103126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Vogel U, Dybdahl M, Frentz G, Nexo BA (2000) DNA repair capacity: inconsistency between effect of over-expression of five NER genes and the correlation to mRNA levels in primary lymphocytes. Mutat Res 461:197–210. https://doi.org/10.1016/s0921-8777(00)00051-3

    Article  CAS  PubMed  Google Scholar 

  12. Compe E, Pangou E, Le May N, Elly C, Braun C, Hwang JH, Coin F, Sumara I, Choi KW, Egly JM (2022) Phosphorylation of XPD drives its mitotic role independently of its DNA repair and transcription functions. Sci Adv 8:eabp9457. https://doi.org/10.1126/sciadv.abp9457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Franczyk B, Gluba-Brzózka A, Olszewski R, Parolczyk M, Rysz-Górzyńska M, Rysz J (2022) miRNA biomarkers in renal disease. Int Urol Nephrol 54:575–588. https://doi.org/10.1007/s11255-021-02922-7

    Article  CAS  PubMed  Google Scholar 

  14. Mutlu T, Ozoran E, Trabulus DC, Talu CK, Erhan D, Mete M, Guven M (2022) Expression of genes related to iron homeostasis in breast cancer. Mol Biol Rep 50:5157–5163. https://doi.org/10.1007/s11033-023-08433-1

    Article  CAS  Google Scholar 

  15. Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JH (2014) Understanding nucleotide excision repair and its roles in cancer and ageing. Nat Rev Mol Cell Biol 15:465–481. https://doi.org/10.1038/nrm3822

    Article  CAS  PubMed  Google Scholar 

  16. Kralund HH, Ousager L, Jaspers NG, Raams A, Pedersen EB, Gade E, Bygum A (2013) Xeroderma Pigmentosum-Trichothiodystrophy overlap patient with novel XPD/ERCC2 mutation. Rare Dis 1:e24932. https://doi.org/10.4161/rdis.24932

    Article  PubMed  PubMed Central  Google Scholar 

  17. Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, Butler A et al (2010) Systematic sequencingn of renal carcinoma reveals inactivation of histone modifying genes. Nature 463:360–363. https://doi.org/10.1038/nature08672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kondo D, Noguchi A, Tamura H, Tsuchida S, Takahashi I, Kubot H, Yano T, Oyama C, Sawaishi Y, Moriwaki S, Takahashi T (2016) Elevated urinary levels of 8-Hydroxy-2’-deoxyguanosine in a japanese child of Xeroderma Pigmentosum/Cockayne Syndrome Complex with Infantile Onset of Nephrotic Syndrome. Tohoku J Exp Med 239:231–235. https://doi.org/10.1620/tjem.239.231

    Article  CAS  PubMed  Google Scholar 

  19. Corredor Z, da Silva Filho MI, Rodríguez-Ribera L, Catalano C, Hemminki K, Coll E, Silva I, Diaz JM, Ballarin JA, Henández A, Försti A, Marcos R, Pastor S (2020) Loci associated with genomic damage levels in chronic kidney disease patients and controls. Mutat Res Genet Toxicol Environ Mutagen 852:503167. https://doi.org/10.1016/j.mrgentox.2020.503167

    Article  CAS  PubMed  Google Scholar 

  20. Radwan WM, Elbarbary HS, Alsheikh NM (2015) DNA repair genes XPD and XRCC1 polymorphisms and risk of end-stage renal disease in egyptian population. Ren Fail 37:122–128. https://doi.org/10.3109/0886022X.2014.967646

    Article  CAS  PubMed  Google Scholar 

  21. Shi S, Yu L, Chiu C, Sun Y, Chen J, Khitrov G, Merkenschlager M, Holzman LB, Zhang W, Mundel P, Bottinger EP (2008) Podocyteselective deletion of dicer induces proteinuria and glomerulosclerosis. J Am Soc Nephrol 19:2159–2169. https://doi.org/10.1681/ASN.2008030312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ho J, Ng KH, Rosen S, Dostal A, Gregory RI, Kreidberg JA (2008) Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J Am Soc Nephrol 19:2069–2075. https://doi.org/10.1681/ASN.2008020162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chen NX, Kiattisunthorn K, O’Neill KD, Chen X, Moorthi RN, Gattone VH, Allen MR, Moe SM (2013) Decreased microRNA is involved in the vascular remodeling abnormalities in chronic kidney disease (CKD). PLoS ONE 8:e64558. https://doi.org/10.1371/journal.pone.0064558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Xu W, Hua Y, Deng F, Wang D, Wu Y, Zhang W, Tang J (2020) MiR-145 in cancer therapy resistance and sensitivity: a comprehensive review. Cancer Sci 111:3122–3131. https://doi.org/10.1111/cas.14517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wei S, Xue J, Sun B, Zou Z, Chen C, Liu Q, Zhang A (2018) miR-145 via targeting ERCC2 is involved in arsenite-induced DNA damage in human hepatic cells. Toxicol Lett 295:220–228. https://doi.org/10.1016/j.toxlet.2018.04.028

    Article  CAS  PubMed  Google Scholar 

  26. Phulkerd T, Lertussavavivat T, Limothai U, Peerapornratana S, Kulvichit W, Lumlertgul N, Tungsanga K, Eiam-Ong S, Avihingsanon Y, Srisawat N (2022) Circulating and urinary microRNAs profile for predicting renal recovery from severe acute kidney injury. J Intensive Care 10:45. https://doi.org/10.1186/s40560-022-00637-0

    Article  PubMed  PubMed Central  Google Scholar 

  27. Park S, Moon S, Lee K, Park IB, Lee DH, Nam S (20189 urinary and blood microRNA-126 and – 770 are potential noninvasive biomarker candidates for diabetic nephropathy: a meta-analysis. Cell Physiol Biochem 46: 1331–1340. https://doi.org/10.1159/000489148

  28. Wang L, Li H (2020) MiR-770-5p facilitates podocyte apoptosis and inflammation in diabetic nephropathy by targeting TIMP3. Biosci Rep 40:BSR20193653. https://doi.org/10.1042/BSR20193653

    Article  PubMed  PubMed Central  Google Scholar 

  29. Zhao H, Yu X, Ding Y, Zhao J, Wang G, Wu X, Jiang J, Peng C, Guo GZ, Cui S (2016) MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2. Oncotarget 7:53254–53268. https://doi.org/10.18632/oncotarget.10736

    Article  PubMed  PubMed Central  Google Scholar 

  30. Bagatini PB, Palazzo RP, Rodrigues MT, Costa CH, Maluf SW (2008) Induction and removal of DNA damage in blood leukocytes of patients with type 2 diabetes mellitus undergoing hemodialysis. Mutat Res 657:111–115. https://doi.org/10.1016/j.mrgentox.2008.08.004

    Article  CAS  PubMed  Google Scholar 

  31. Muller C, Eisenbrand G, Gradinger M, Rath T, Albert FW, Vienken J, Singh R, Farmer PB, Stockis JP, Janzowski C (2004) Effects of hemodialysis, dialyser type and iron infusion on oxidative stress in uremic patients. Free Radic Res 38:1093–1100. https://doi.org/10.1080/10715760400011452

    Article  CAS  PubMed  Google Scholar 

  32. Comoglu M, Dede F, Yenigun EC, Topcuoglu C, Inan O, Sahiner ES, Ates I (2022) Effects of medium cutoff membranes on pro-inflammatory cytokine and oxidative marker levels in patients with sepsis who developed acute kidney injury. Blood Purif 51:772–779. https://doi.org/10.1159/000519881

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Scientific Research Project Coordination Unit of Istanbul University-Cerrahpasa funded the research, Project No. 35624.

Author information

Authors and Affiliations

  1. Department of Medical Biology, Cerrahpasa Medicine Faculty, Istanbul University-Cerrahpasa, Istanbul, 34098, Turkey

    Elif Citak & Mehmet Guven

  2. Department of Nephrology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey

    Serkan Feyyaz Yalin

  3. Department of Nephrology, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey

    Mehmet Riza Altiparmak

Authors
  1. Elif Citak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Serkan Feyyaz Yalin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mehmet Riza Altiparmak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mehmet Guven
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehmet Guven.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethics approval and consent to participate

The ethical approval was obtained from Istanbul University-Cerrahpasa Cerrahpasa Medical School Institutional Review Board with the serial code of 23,992. All of the procedures on human participants were in accordance with the declaration of Helsinki in 1964, its ammendments and parallel ethical standards.

Consent for publication

All the patients in this study provided informed consent before inclusion.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Citak, E., Yalin, S.F., Altiparmak, M.R. et al. Investigation of XPD, miR-145 and miR-770 expression in patients with end-stage renal disease. Mol Biol Rep 50, 6843–6850 (2023). https://doi.org/10.1007/s11033-023-08608-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-023-08608-w

Keywords

Search

Navigation