Investigation of LncRNAs expression in patients with hepatitis B virus

Cansu Önlen Güneri 1 * , Hamza Malik Okuyan 2, Gülay Gülbol Duran 3, Mehmet Demir 4
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1 Department of Medical Laboratory Techniques, Gulhane Vocational School of Health Services, University of Health Sciences, Ankara, Turkey
2 Faculty of Health Sciences, Sakarya University of Applied Sciences, Sakarya, Turkey
3 Basic Medical Sciences, Department of Medical Biology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
4 Internal Medicine Sciences, Department of Gastroenterology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
* Corresponding Author
J CLIN MED KAZ, Volume 19, Issue 6, pp. 27-31. https://doi.org/10.23950/jcmk/12662
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ABSTRACT

Aim: Patients infected with the hepatitis B virus (HBV) are at a higher risk of cirrhosis and hepatocellular carcinoma. Despite the recent advancement of antiviral therapy, many patients still cannot respond to existing therapies. Hence, to detect the changes in liver function earlier, non-invasive methods are needed. Long non-coding RNAs (lncRNAs) play important roles in essential biological process as well as human cancer. LncRNAs may be used as biomarkers in human diseases. Thus, in this study, we purposed to analyze the expression levels of lncRNAs (HOX transcript antisense RNA (HOTAIR), maternally expressed 3 (MEG-3), highly upregulated in liver cancer (HULC)) in patients with hepatitis B virus and healthy volunteers.
Methods: We selected three lncRNAs as candidate lncRNAs based on their association with liver disease. Whole blood samples were collected from 40 patients with HBV and 48 healthy volunteers. The expression levels of all the samples were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis was implemented using GraphPad Prism software. A p-value lower than 0.05 was statistically meaningful.
Results: The expression levels of HOTAIR and HULC were remarkably upregulated in the plasma of the patients with HBV compared with healthy control (p<0.05). In contrast, no significant difference in MEG-3 expression levels was observed between groups.
Conclusion: Our findings showed that the expression of HOTAIR and HULC in plasma might be new promising diagnostic and/or prognostic biomarkers for HBV.
Keywords: long noncoding RNA, hepatitis B virus, HOTAIR, HULC

CITATION

Önlen Güneri C, Okuyan HM, Gülbol Duran G, Demir M. Investigation of LncRNAs expression in patients with hepatitis B virus. J CLIN MED KAZ. 2022;19(6):27-31. https://doi.org/10.23950/jcmk/12662

REFERENCES

  • World Health Organization (WHO) Hepatitis B. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b.
  • Ringehan M, McKeating JA, Protzer U. Viral hepatitis and liver cancer. Philos Trans R Soc Lond B Biol Sci. 2017; 372(1732): 20160274. https://doi.org/10.1098/rstb.2016.0274
  • Alexander J., Kowdley KV. Epidemiology of Hepatitis B–Clinical Implications. MedGenMed. 2006;8(2):13.
  • Leblebicioglu H, Eroglu C. Members of the Hepatitis Study Group. Acute hepatitis B virus infection in Turkey: epidemiology and genotype distribution. Clin Microbiol Infect. 2004; 10: 537–541. https://doi.org/10.1111/j.1469-0691.2004.00871.x
  • Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B Cure: From Discovery to Regulatory Approval. Hepatology. 2017; 66(4): 1296–1313. https://doi.org/10.1002/hep.29323
  • Ren F, Ren JH, Song CL. LncRNA HOTAIR modulates hepatitis B virus transcription and replication by enhancing SP1transcription factor. Clinical Science. 2020; 134:3007–3022. https://doi.org/10.1042/CS20200970
  • Yu J, Zhang H, Zhan Y, Zhang X. Integrated Analysis of the Altered lncRNA, microRNA, and mRNA Expression in HBV-Positive Hepatocellular Carcinoma. Life. 2022; 12, 701. https://doi.org/10.3390/life12050701
  • Samudh N, Shrilall C, Arbuthnot P, Bloom K and Ely A. Diversity of Dysregulated Long Non-Coding RNAs in HBV-Related Hepatocellular Carcinoma. Front. Immunol. 2022; 13:834650. https://doi.org/10.3389/fimmu.2022.834650
  • Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nature Reviews. 2021; 22 96-118. https://doi.org/10.1038/s41580-020-00315-9
  • Li L, Chang HY. Physiological roles of long noncoding RNAs: Insights from knockout mice. Trends Cell Biol. 2014; 24(10): 594–602. https://doi.org/10.1016/j.tcb.2014.06.003
  • Yoon JH., Abdelmohsen K., Gorospe M. Post-transcriptional gene regulation by long noncoding RNA. J Mol Biol. 2013; 425(19): 3723–3730. https://doi.org/10.1016/j.jmb.2012.11.024
  • Mercer TR., Dinger ME., and Mattick JS. Long non-coding RNAs: insights into functions. Nature Reviews Genetics. 2009; 10(3):155–159.
  • Rossi MN., Antonangeli F. LncRNAs: New Players in Apoptosis Control. International Journal of Cell Biology. 2014, Article ID 473857, 7 pages. http://dx.doi.org/10.1155/2014/4738577
  • Ouyang J., Hu J., Chen JL. lncRNAs regulate the innate immune response to viral infection. WIREs RNA. 2016; 7:129–143. https://doi.org/10.1002/wrna.1321
  • Gupta RA., Shah N, Wang KC. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010; 464(7291):1071–1076. https://doi.org/10.1038/nature08975
  • Lin R, Maeda S, Liu C, Karin M, and Edgington TS. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene. 2007; 26(6):851–858. https://doi.org/10.1038/sj.onc.1209846
  • Liu Y, Pan S, Liu L. A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population. PLoS ONE. 2012; 7(4). Article ID e35145. https://doi.org/10.1371/journal.pone.0035145
  • Fortes P, Morris K. Long noncoding RNAs in viral infections. Virus Res. 2016; 212: 1–11. https://doi.org/10.1016/j.virusres.2015.10.002
  • Zhao Y, Fan Y, Wang K, et al. LncRNA HULC affects the differentiation of Treg in HBV-relatedlivercirrhosis. IntImmunopharmacol. 2015;28:901-905. https://doi.org/10.1016/j.intimp.2015.04.028
  • Panzitt K, Tschernatsch MMO, Guelly C. et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 2007; 132(1):330–342. https://doi.org/10.1053/j.gastro.2006.08.026
  • Zhou Y, Zhang X, Klibanski A. MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol. 2012;48: R45- R53. https://doi.org/10.1530/JME-12-0008
  • Dong Z, Zhang A, Liu S, Lu F, Guo Y, Zhang G, Xu F, Shi Y, Shen S, Liang J, Guo W. Aberrant methylation-mediated silencing of lncRNA MEG3 functions as a ceRNA in esophageal cancer. Mol Cancer Res. 2017;15:800-810. https://doi.org/10.1158/1541-7786.MCR-16-0385
  • Chen MJ, Wang XG, Sun ZX, Liu XC. Diagnostic value of LncRNA-MEG3 as a serum biomarker in patients with hepatitis B complicated with liver fibrosis. European Review for Medical and Pharmacological Sciences. 2019;23:4360-4367.
  • Wang WT, Ye H, Wei PP, Han BW, He B, Chen ZH, et al. LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner. J Hematol Oncol. 2016; 9:117. https://doi.org/10.1186/s13045-016-0348-0