A study of serum miRNA-122 in hepatitis C and associated hepatocellular carcinoma

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  • Authors: Yushchuk N.D.1, Malov S.I.2,3, Malov I.V2, Dvornichenko V.V.2, Rasulov R.I.3, Marche P.4, Decaens T.4,5, Macek-Jilkova Z.4,5, Stepanenko L.A.2, Ogarkov O.B.6, Orlova L.S.2
  • Affiliations:
    1. A.I. Evdokimov Moscow State University of Medicine and Dentistry
    2. Irkutsk State Medical University
    3. Irkutsk State Medical Academy of Postgraduate Education
    4. Institute for Advanced Biosciences, Research Center, University of Grenoble-Alpes
    5. Hospital Center of University of Grenoble-Alpes
    6. Scientific Center of Family Health and Human Reproduction
  • Issue: Vol 74, No 6 (2019)
  • Pages: 388-395
  • Section: INFECTIOUS DISEASES: CURRENT ISSUES
  • URL: https://vestnikramn.spr-journal.ru/jour/article/view/1255
  • DOI: https://doi.org/10.15690/vramn1255
  • Cite item
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Abstract


BACKGROUND: The discovery of a cluster of short non-coding RNAs called microRNAs (miRNAs) has become an important event in molecular biology. One of its representatives, miR-122 plays a large role in regulating the expression of genes involved in carbohydrate, lipid metabolism, and iron metabolism in the body. In experimental studies it was shown that in addition to regulatory functions, miR-122 is involved in the pathogenesis of hepatitis C, providing the life cycle of the virus in the cell. The shift of emphasis in the study of miR-122 from basic research into clinical medicine seems to be a promising area of personalized medicine.

AIMS: to determine the clinical significance of miR-122 in acute and chronic hepatitis C and associated hepatocellular carcinoma.

MATERIALS AND METHODS: A total of 407 people were examined, including 17 patients with acute hepatitis C (AHC), 158 patients with chronic hepatitis C (CHC) and 62 patients with HCC associated with hepatitis C. Comparison groups consisted of 84 healthy individuals and 62 patients with clinically pronounced cirrhosis of a non-infectious etiology. In each cohort, the relative miR-122 level was determined in the blood of patients. The analysis was performed in PCR using the Qubit microRNA Assay Kit -100 for the quantitative determination of microRNAs (Thermo Fisher Scientific, USA). Relative miR-122 expression values were calculated by the formula 2 -ΔΔCT using U6 snRNA as a reference RNA.

RESULTS: The highest miR-122 level in serum was found in patients with AHC at the height of the icteric period. The level of miR-122 showed a direct correlation with the activity of hepatic transaminases in patients with AHC (r = 0.72) and CHC (r = 0.44). An analysis of miR-122 level relative to the degree of liver fibrosis in patients with chronic hepatitis C showed that, as liver fibrosis progresses, the level of miR-122 expression decreases. The decrease in miR-122 expression in patients with severe fibrosis was universal and did not depend on the etiology of the disease. The development of HCC in the presence of chronic hepatitis C was accompanied by a decrease in the level of miR-122 by 10 times on average compared to patients with chronic hepatitis C.

CONCLUSIONS: The determination of the expression level of miR-122 in serum can be used in laboratory monitoring of the management of patients with HC as an indicator of the severity of liver damage in AHC and the rate of formation of liver fibrosis in CHC. Evaluation of possibility of using miR-122 as a predictor of the development of HCC in the outcome of HC requires additional studies of the specificity and sensitivity of the test and comparison of the obtained data with the results of using generally accepted protein tumor markers.


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About the authors

Nikolay D. Yushchuk

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Email: prof.uyshuk@gmail.com
ORCID iD: 0000-0003-1928-4747
SPIN-code: 8547-6651

Russian Federation, 20/1, Delegatskaya street, Moscow, 127473

MD, PhD

Sergey I. Malov

Irkutsk State Medical University; Irkutsk State Medical Academy of Postgraduate Education

Author for correspondence.
Email: LYNX2000@mail.ru
ORCID iD: 0000-0002-3135-4616
SPIN-code: 5050-3112

Russian Federation, 1, krasnogo vosstaniya st., Irkutsk, 664003; 100, Yubileinyi mkr, Irkutsk, 664049

MD

Igor V Malov

Irkutsk State Medical University

Email: igmumalov@gmail.com
ORCID iD: 0000-0002-0122-4618
SPIN-code: 8302-3057

Russian Federation, 1, krasnogo vosstaniya st., Irkutsk, 664003

MD, PhD

Viktoriya V. Dvornichenko

Irkutsk State Medical University

Email: vv.dvornichenko@gmail.com
ORCID iD: 0000-0002-1777-5449
SPIN-code: 9628-8656

Russian Federation, 1, krasnogo vosstaniya st., Irkutsk, 664003

MD, PhD

Rodion I. Rasulov

Irkutsk State Medical Academy of Postgraduate Education

Email: gava2010@yandex.ru
ORCID iD: 0000-0002-3671-1459
SPIN-code: 3520-6049

Russian Federation, 100, Yubileinyi mkr., Irkutsk, 664049

MD, PhD

Patrice N. Marche

Institute for Advanced Biosciences, Research Center, University of Grenoble-Alpes

Email: patrice.marche@inserm.fr
ORCID iD: 0000-0002-8930-9340

France, La Tronche

PhD

Thomas Decaens

Institute for Advanced Biosciences, Research Center, University of Grenoble-Alpes; Hospital Center of University of Grenoble-Alpes

Email: tdecaens@chu-grenoble.fr
ORCID iD: 0000-0003-0928-0048

France, La Tronche

PhD department of hepatogastroenterology

Zuzana Macek-Jilkova

Institute for Advanced Biosciences, Research Center, University of Grenoble-Alpes; Hospital Center of University of Grenoble-Alpes

Email: zuzana.mjilkova@gmail.com
ORCID iD: 0000-0002-2553-5971

France, La Tronche

PhD department of hepatogastroenterology

Liliya A. Stepanenko

Irkutsk State Medical University

Email: steplia@mail.ru
ORCID iD: 0000-0002-5792-7283
SPIN-code: 1148-6958

Russian Federation, 1, krasnogo vosstaniya st., Irkutsk, 664003

MD

Oleg B. Ogarkov

Scientific Center of Family Health and Human Reproduction

Email: obogarkov@mail.ru
ORCID iD: 0000-0002-3168-1983
SPIN-code: 1956-2888

Russian Federation, 16, Timiryazeva street, Irkutsk, 664003

MD, PhD

Larisa S. Orlova

Irkutsk State Medical University

Email: orlovalarisas@gmail.com
ORCID iD: 0000-0002-2248-6940
SPIN-code: 7538-0290

Russian Federation, 16, Timiryazeva street, Irkutsk, 664003

MD

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Supplementary files

Supplementary Files Action
1.
Fig. 1. Correlation of alanine aminotransferase (ALT) activity with blood miR-122 level in acute hepatitis C (n = 17)

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2.
Fig. 2. Correlation of alanine aminotransferase (ALT) activity with blood miR-122 level in chronic hepatitis C (n = 17)

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3.
Fig. 3. Change in miR-122 level during the progression of fibrosis and the transformation of chronic hepatitis C (CHC) into hepatocellular carcinoma (HCC)

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4.
Fig. 4. The level of miR-122 depending on the degree of liver fibrosis in patients with chronic hepatitis C (CHC) and cirrhosis of the liver of non-infectious etiology

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