---
title: "MicroRNA-122: Regulator and Biomarker Across Liver Disease Spectrum"
id: "pubmed-42760391"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42760391"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42760391/"
doi: "10.1007/s00109-026-02718-1"
published_at: "2026-09-19T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# MicroRNA-122: Regulator and Biomarker Across Liver Disease Spectrum
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42760391
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42760391/)
- **DOI:** [10.1007/s00109-026-02718-1](https://doi.org/10.1007%2Fs00109-026-02718-1)
- **Published At:** 2026-09-19T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- **miR-122** is the dominant liver-specific microRNA, representing about 70% of the hepatic miRNA pool and acting as a central regulator of lipid metabolism, inflammation, fibrosis, viral replication, and hepatocarcinogenesis. - Experimental and clinical evidence link miR-122 to metabolic dysfunction-associated fatty liver disease (MAFLD) and steatohepatitis (MASH), drug-induced acute liver injury, HBV and HCV infection, hepatocellular carcinoma (HCC), and colorectal cancer liver metastasis. - Mechanistic pathways include control of hepatic lipogenesis via the **Sirt1/LKB1/AMPK** axis and modulation of inflammation through **LPS/TLR-4/FoxO3** signaling. - Tumor-suppressive and antiviral roles are mediated through multiple targets and pathways such as **Cyclin G1/p53**, **HO-1**, **NDRG3**, **GALNT10**, **PEG10**, and **NEGR1**. - A key theme is compartment- and stage-dependent expression: hepatic **miR-122** declines with disease progression, while circulating **miR-122** increases with hepatocyte injury, which affects biomarker interpretation depending on specimen source and disease stage. - Etiology-specific regulation differs between HBV and HCV: HBV-associated changes involve epigenetic silencing, whereas interferon-linked mechanisms drive HCV-associated regulation. - Clinical translation of anti-miR-122 therapies (miravirsen, RG-101) has failed to advance due to viral resistance, safety concerns, and a tumor-suppressor paradox that complicates inhibition strategies. - Overall, **miR-122** is a promising minimally invasive **biomarker** and a biologically informative but therapeutically challenging target in liver disease.
## Clinical Analysis & Structured Key Points
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MicroRNA-122 as a regulator and biomarker of liver disease [Sara Ahmadova](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmadova+S&cauthor_id=42760391)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-1 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-2 "Doctoral School, Medical University of Warsaw, Warsaw, Poland."), [Zofia Wicik](https://pubmed.ncbi.nlm.nih.gov/?term=Wicik+Z&cauthor_id=42760391)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-1 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-3 "Department of Experimental and Clinical Neuroscience, Institute of Psychiatry and Neurology, Warsaw, 02-957, Poland."), [Joanna Mucha](https://pubmed.ncbi.nlm.nih.gov/?term=Mucha+J&cauthor_id=42760391)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-1 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-4 "Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences-SGGW, 02-787, Warsaw, Poland."), [Jeff Palatini](https://pubmed.ncbi.nlm.nih.gov/?term=Palatini+J&cauthor_id=42760391)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-5 "Genomics Core Facility, Centre of New Technologies, University of Warsaw, Warsaw, Poland."), [Katarzyna Ziętal](https://pubmed.ncbi.nlm.nih.gov/?term=Zi%C4%99tal+K&cauthor_id=42760391)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-1 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland."), [Dagmara Mirowska-Guzel](https://pubmed.ncbi.nlm.nih.gov/?term=Mirowska-Guzel+D&cauthor_id=42760391)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-1 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland."), [Adam Przybylkowski](https://pubmed.ncbi.nlm.nih.gov/?term=Przybylkowski+A&cauthor_id=42760391)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-6 "Gastroenterology Department, Medical University of Warsaw, Warsaw, Poland."), [Ceren Eyileten](https://pubmed.ncbi.nlm.nih.gov/?term=Eyileten+C&cauthor_id=42760391)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-7 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland. ceyileten@wum.edu.pl.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#full-view-affiliation-8 "Department of Anesthesiology, Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, PAus, Hershey, 17033, USA. ceyileten@wum.edu.pl.") Affiliations Expand ### Affiliations * 1 Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland. * 2 Doctoral School, Medical University of Warsaw, Warsaw, Poland. * 3 Department of Experimental and Clinical Neuroscience, Institute of Psychiatry and Neurology, Warsaw, 02-957, Poland. * 4 Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences-SGGW, 02-787, Warsaw, Poland. * 5 Genomics Core Facility, Centre of New Technologies, University of Warsaw, Warsaw, Poland. * 6 Gastroenterology Department, Medical University of Warsaw, Warsaw, Poland. * 7 Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland. ceyileten@wum.edu.pl. * 8 Department of Anesthesiology, Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, PAus, Hershey, 17033, USA. ceyileten@wum.edu.pl. * PMID: **42760391** * DOI: [ 10.1007/s00109-026-02718-1 ](https://doi.org/10.1007/s00109-026-02718-1) Item in Clipboard Review # MicroRNA-122 as a regulator and biomarker of liver disease Sara Ahmadova et al. J Mol Med (Berl). 2026. Show details Display options Display options Format Abstract PubMed PMID J Mol Med (Berl) Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Mol+Med+%28Berl%29%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Mol+Med+%28Berl%29%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42760391/) . 2026 Sep 19;104(1):110. doi: 10.1007/s00109-026-02718-1. ### Authors [Sara Ahmadova](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmadova+S&cauthor_id=42760391)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-1 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-2 "Doctoral School, Medical University of Warsaw, Warsaw, Poland."), [Zofia Wicik](https://pubmed.ncbi.nlm.nih.gov/?term=Wicik+Z&cauthor_id=42760391)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-1 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-3 "Department of Experimental and Clinical Neuroscience, Institute of Psychiatry and Neurology, Warsaw, 02-957, Poland."), [Joanna Mucha](https://pubmed.ncbi.nlm.nih.gov/?term=Mucha+J&cauthor_id=42760391)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-1 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-4 "Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences-SGGW, 02-787, Warsaw, Poland."), [Jeff Palatini](https://pubmed.ncbi.nlm.nih.gov/?term=Palatini+J&cauthor_id=42760391)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-5 "Genomics Core Facility, Centre of New Technologies, University of Warsaw, Warsaw, Poland."), [Katarzyna Ziętal](https://pubmed.ncbi.nlm.nih.gov/?term=Zi%C4%99tal+K&cauthor_id=42760391)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-1 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland."), [Dagmara Mirowska-Guzel](https://pubmed.ncbi.nlm.nih.gov/?term=Mirowska-Guzel+D&cauthor_id=42760391)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-1 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland."), [Adam Przybylkowski](https://pubmed.ncbi.nlm.nih.gov/?term=Przybylkowski+A&cauthor_id=42760391)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-6 "Gastroenterology Department, Medical University of Warsaw, Warsaw, Poland."), [Ceren Eyileten](https://pubmed.ncbi.nlm.nih.gov/?term=Eyileten+C&cauthor_id=42760391)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-7 "Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland. ceyileten@wum.edu.pl.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42760391/#short-view-affiliation-8 "Department of Anesthesiology, Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, PAus, Hershey, 17033, USA. ceyileten@wum.edu.pl.") ### Affiliations * 1 Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland. * 2 Doctoral School, Medical University of Warsaw, Warsaw, Poland. * 3 Department of Experimental and Clinical Neuroscience, Institute of Psychiatry and Neurology, Warsaw, 02-957, Poland. * 4 Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences-SGGW, 02-787, Warsaw, Poland. * 5 Genomics Core Facility, Centre of New Technologies, University of Warsaw, Warsaw, Poland. * 6 Gastroenterology Department, Medical University of Warsaw, Warsaw, Poland. * 7 Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Banacha 1B, 02-097, Warsaw, Poland. ceyileten@wum.edu.pl. * 8 Department of Anesthesiology, Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, PAus, Hershey, 17033, USA. ceyileten@wum.edu.pl. * PMID: **42760391** * DOI: [ 10.1007/s00109-026-02718-1 ](https://doi.org/10.1007/s00109-026-02718-1) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract MicroRNA-122 (miR-122) is the most abundant liver-specific microRNA, comprising ~ 70% of the hepatic miRNA pool, and a central regulator of lipid metabolism, inflammation, fibrosis, viral replication, and hepatocarcinogenesis. This review synthesizes experimental, clinical, and molecular evidence on the role of miR-122 across the spectrum of liver disease, including metabolic dysfunction-associated fatty liver disease (MAFLD) and steatohepatitis (MASH), drug-induced acute liver injury, hepatitis B and C virus (HBV/HCV) infection, hepatocellular carcinoma (HCC), and colorectal cancer liver metastasis. Mechanistically, miR-122 governs hepatic lipogenesis through the Sirt1/LKB1/AMPK axis, modulates inflammation via LPS/TLR-4/FoxO3 signaling, and exerts tumor-suppressive and antiviral effects through Cyclin G1/p53, HO-1, NDRG3, GALNT10, PEG10, and NEGR1. A recurring theme is the compartment- and stage-dependent behavior of miR-122: hepatic expression declines with disease progression, whereas circulating levels rise with hepatocyte injury, reconciling apparently contradictory reports and underscoring the importance of specimen source and disease stage in biomarker interpretation. We further contrast the etiology-specific regulation of miR-122 in HBV- versus HCV-associated disease, in which epigenetic silencing and interferon-linked mechanisms drive divergent expression. Finally, we critically appraise the failed clinical translation of anti-miR-122 therapeutics (miravirsen, RG-101), highlighting viral resistance, safety liabilities, and the tumor-suppressor paradox that constrains inhibition-based strategies. Collectively, miR-122 emerges as a minimally invasive biomarker and a biologically informative, though therapeutically challenging, target in liver disease. **Keywords:** Biomarker; Fibrosis; Hepatitis B virus (HBV); Hepatitis C virus (HCV); Hepatocellular carcinoma (HCC); Lipid metabolism; Metabolic dysfunction-associated fatty liver disease (MAFLD); Metabolic dysfunction-associated steatohepatitis (MASH); MiR-122; Therapeutic target. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Ethics approval and consent to participate: Not applicable. Patient consent for publication: Not applicable. Conflict of interests: The authors declare that they have no competing interests. ## References 1. 1. Yang Z, Wu W, Ou P et al (2021) MiR-122-5p knockdown protects against APAP-mediated liver injury through up-regulating NDRG3. Mol Cell Biochem 476:1257–1267 - [DOI](https://doi.org/10.1007/s11010-020-03988-0) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/33247804/) 2. 1. Roderburg C, Benz F, Vargas Cardenas D et al (2015) Elevated miR-122 serum levels are an independent marker of liver injury in inflammatory diseases. Liver Int 35:1172–1184 - [DOI](https://doi.org/10.1111/liv.12627) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/25039534/) 3. 1. Hofstraat SHI, Falla AM, Duffell EF et al (2017) Current prevalence of chronic hepatitis B and C virus infection in the general population, blood donors and pregnant women in the EU/EEA: a systematic review. Epidemiol Infect 145:2873–2885 - [DOI](https://doi.org/10.1017/s0950268817001947) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/28891457/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/5647665/) 4. 1. Hayes CN, Akamatsu S, Tsuge M et al (2012) Hepatitis B virus-specific miRNAs and Argonaute2 play a role in the viral life cycle. PLoS One 7:e47490 - [DOI](https://doi.org/10.1371/journal.pone.0047490) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/23091627/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/3472984/) 5. 1. Coulouarn C, Factor VM, Andersen JB et al (2009) Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene 28:3526–3536 - [DOI](https://doi.org/10.1038/onc.2009.2
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