Comparison of Mir122 expression in children with biliary atresia and healthy group

Document Type : Original article

Authors

1 Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran

3 Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

4 Cardiovascular Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran

5 Otolaryngology Research Center, Department of Otolaryngology, Shiraz University of Medical Sciences, Shiraz, Iran

6 Abu-Ali Sina Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Biliary atresia (BA) is the primary cause of neonatal jaundice with various pathological mechanisms. Many BA patients may experience progressive liver dysfunction and eventually need a liver transplant. Therefore, identifying potential non-invasive biomarkers for BA is crucial. miR-122, the most abundant microRNA in the liver, plays significant roles in different liver diseases. This study aimed to assess miR-122 levels in BA patients. Eighteen patients with biliary atresia were selected at random from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), along with 18 healthy controls. Blood samples were collected, and biochemical parameters (such as liver function tests) were measured. Quantitative reverse-transcription PCR (RT-PCR) was conducted on serum samples from both the case and control groups to analyze miR-122 levels. The study results indicated that serum miR-122 expression in BA patients was elevated compared to the control group, although it did not reach statistical significance. Additionally, no correlation was found between miR-122 expression and serum levels of liver enzymes or other laboratory findings in BA cases. miR-122 could be a potential target for diagnosing BA; however, further research with a larger population is necessary to determine if miR-122 could serve as a useful biomarker for diagnosing BA.

Keywords

References

  1. Vij M, Rela M. Biliary atresia: pathology, etiology and pathogenesis. Future Sci OA 2020; 6:FSO466.
  2. Makhmudi A, Kalim AS. Gunadi. microRNA-21 expressions impact on liver fibrosis in biliary atresia patients. BMC Res Notes 2019;12:189.
  3. Lendahl U, Lui VCH, Chung PHY, Tam PKH. Biliary Atresia–emerging diagnostic and therapy opportunities. EBioMedicine 2021;74:103689.
  4. Sanchez-Valle A, Kassira N, Varela VC, Radu SC, Paidas C, Kirby RS. Biliary atresia: epidemiology, genetics, clinical update, and public health perspective. Adv Pediatr 2017; 64:285-305.
  5. Lakshminarayanan B, Davenport M. Biliary atresia: A comprehensive review. J Autoimmun 2016;73:1-9.
  6. Bezerra JA, Wells RG, Mack CL, Karpen SJ, Hoofnagle JH, Doo E, Sokol RJ. Biliary atresia: clinical and research challenges for the twenty‐first century. Hepatology 2018;68: 1163-1173.
  7. Ye Y, Li Z, Feng Q, Chen Z, Wu Z, Wang J, Ye X, Zhang D, Liu L, Gao W, Zhang L, Wang B. Downregulation of microRNA-145 may contribute to liver fibrosis in biliary atresia by targeting ADD3. PLoS One 2017;12:e0180896.
  8. Kasahara M, Umeshita K, Sakamoto S, Fukuda A, Furukawa H, Uemoto S. Liver transplantation for biliary atresia: a systematic review. Pediatr Surg Int 2017;33:1289-1295.
  9. Nan Y, Niu X, Wang R, Zhao S, Fu N, Du J, Wang Y, Wang B, Zhang Y. microRNA‑1273g‑3p is a useful non‑invasive test for the prediction of liver fibrosis in patients with chronic hepatitis C. Exp Ther Med 2019;17:1817-1824.
  10. Yamada H, Ohashi K, Suzuki K, Munetsuna E, Ando Y, Yamazaki M, Ishikawa H, Ichino N, Teradaira R, Hashimoto S. Longitudinal study of circulating miR-122 in a rat model of non-alcoholic fatty liver disease. Clin Chim Acta 2015;446:267-271.
  11. Boutz DR, Collins PJ, Suresh U, Lu M, Ramírez CM, Fernández-Hernando C, Huang Y, Abreu R de S, Le SY, Shapiro BA, Liu AM, Luk JM, Aldred SF, Trinklein ND, Marcotte EM, Penalva LOF. Two-tiered approach identifies a network of cancer and liver disease-related genes regulated by miR-122. J Biol Chem 2011;286:18066-18078.
  12. Otsuka M, Kishikawa T, Yoshikawa T, Yamagami M, Ohno M, Takata A, Shibata C, Ishibashi R, Koike K . MicroRNAs and liver disease. J human genet 2017;62:75-80.
  13. Wang S, Qiu L, Yan X, Jin W, Wang Y, Chen L, Wu E, Ye X, Gao GF, Wang F, Chen Y, Duan Z, Meng S. Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G1‐modulated P53 activity. Hepatology 2012;55:730-741.
  14. Long JK, Dai W, Zheng YW, Zhao SP. miR-122 promotes hepatic lipogenesis via inhibiting the LKB1/AMPK pathway by targeting Sirt1 in non-alcoholic fatty liver disease. Mol Med 2019;25:26.
  15. Kang Z, Yang Y, Lu Y, Chen Q, Han R, Lu W, Zhang M, Ma Z, Huang G, Xu H. MiR-196a and miR-122 as potential markers in cholestatic liver disease induced by drugs. Trop J Pharm Res 2021;20:2567-2571.
  16. Liu Y, Li P, Liu L, Zhang Y. The diagnostic role of miR-122 in drug-induced liver injury: a systematic review and meta-analysis. Medicine (Baltimore) 2018;97:e13478.
  17. Motazedian N, Geramizadeh B, Dehghani SM, Azarpira N, Aghdaei MH, Yaghobi R, Shamsaeefar A, Kazemi K, Karimi MH, Mirahmadizadeh A, Mashhadiagha A, Ataollahi M, Ilkhanipoor H, Basiratnia M, Nemati H, Ekramzadeh M, Sanaei Dashti A, Nikeghbalian S, Malekhosseini SA. Cohort Profile: Shiraz Pediatric Liver Cirrhosis Cohort (SPLCCS). Arch Iran Med 2023;26:229-233.
  18. Konings MCJM, Baumgartner S, Mensink RP, Plat J. Investigating microRNAs to Explain the Link between Cholesterol Metabolism and NAFLD in Humans: A Systematic Review. Nutrients 2022;14:4946.
  19. Ho PTB, Clark IM, Le LTT. MicroRNA-based diagnosis and therapy. Int J Mol Sci 2022; 23:7167.
  20. Wang X, He Y, Mackowiak B, Gao B. MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases. Gut 2021;70:784-795.
  21. Zahm AM, Hand NJ, Boateng LA, Friedman JR. Circulating microRNA is a biomarker of biliary atresia. J Pediatr Gastroenterol Nutr 2012;55:366-369.
  22. Murray DD, Suzuki K, Law M, Trebicka J, Nordwall JN, Johnson M, Vjecha MJ, Kelleher AD, Emery S. Circulating miR-122 and miR-200a as biomarkers for fatal liver disease in ART-treated, HIV-1-infected individuals. Sci Rep 2017;7:10934.
  23. Church RJ, Otieno M, McDuffie JE, Singh B, Sonee M, Hall L, Watkins PB, Ellinger-Ziegelbauer H, Harrill AH. Beyond miR-122: identification of MicroRNA alterations in blood during a time course of hepatobiliary injury and biliary hyperplasia in rats. Toxicol Sci 2016;150:3-14.
  24. Calkins KL, Thamotharan S, Ghosh S, Dai Y, Devaskar SU. MicroRNA 122 Reflects Liver Injury in Children with Intestinal Failure-Associated Liver Disease Treated with Intravenous Fish Oil. J Nutr 2020;150:1144-1150.
  25. Peng X, Yang L, Liu H, Pang S, Chen Y, Fu J, Chen Yi, Wen Z, Zhang R, Zhu B, Yu J, Invernizzi P. Identification of circulating microRNAs in biliary atresia by next-generation sequencing. J Pediatr Gastroenterol Nutr 2016;63:518-523.
  26. Smith M, Zuckerman M, Kandanearatchi A, Thompson R, Davenport M. Using next-generation sequencing of microRNAs to identify host and/or pathogen nucleic acid signatures in samples from children with biliary atresia–a pilot study. Access Microbiol 2020;2:acmi000127.
  27. Calvopina DA, Coleman MA, Lewindon PJ, Ramm GA. Function and Regulation of MicroRNAs and Their Potential as Biomarkers in Paediatric Liver Disease. Int J Mol Sci 2016;17:1795.
  28. Murray DD, Suzuki K, Law M, Trebicka J, Nordwall JN, Johnson M, Vjecha,MJ, Kelleher AD, Emery S. Circulating miR-122 and miR-200a as biomarkers for fatal liver disease in ART-treated, HIV-1-infected individuals. Sci Rep 2017;7:10934.
  29. Wu SS. Investigating the Role of MicroRNAs in Human Congenital Hepatic Fibrosis: University of Toronto (Canada) 2014.
  30. Song S, Li X, Geng C, Guo Y, Yang Y, Wang C. Uncovering key molecules and immune landscape in cholestatic liver injury: implications for pathogenesis and drug therapy. Front Pharmacol 2023;14.1171512.
  31. Waidmann O, Köberle V, Brunner F, Zeuzem S, Piiper A, Kronenberger B. Serum microRNA-122 predicts survival in patients with liver cirrhosis. PLoS One 2012;7:e45652.
  32. Calvopina DA, Coleman MA, Lewindon PJ, Ramm GA. Function and regulation of microRNAs and their potential as biomarkers in paediatric liver disease. Int J Mol Sci 2016; 17:1795.
  33. Auguet T, Aragonès G, Berlanga A, Guiu-Jurado E, Martí A, Martínez S, Sabench F, Hernández M, Aguilar C, Sirvent J, Castillo DD, Richart C. miR33a/miR33b* and miR122 as possible contributors to hepatic lipid metabolism in obese women with nonalcoholic fatty liver disease. Int J Mol Sci 2016;17:1620.
  34. Qiu Z, Dai Y. Roadmap of miR-122-related clinical application from bench to bedside. Expert Opin Investig Drugs 2014;23:347-355.
  35. Pirola CJ, Gianotti TF, Castaño GO, Mallardi P, San Martino J, Ledesma MMGL, Flichman D, Mirshahi F, Sanyal AJ, Sookoian S. Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis. Gut 2015;64:800-812.

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