MicroRNA-122 as a regulator and biomarker of liver disease

Sep 22, 2026

Uploaded by moss~

MicroRNA-122 (miR-122) is the most abundant liver-specific microRNA, accounting for about 70% of hepatic microRNAs and acting as a central regulator of lipid metabolism, inflammation, fibrosis, viral replication, and hepatocarcinogenesis. This review integrates experimental, clinical, and molecular evidence across metabolic dysfunction-associated fatty liver disease, viral hepatitis B and C, drug-induced acute injury, hepatocellular carcinoma, and colorectal cancer liver metastasis. It details mechanistic signaling pathways, explains compartment- and stage-dependent biomarker behavior, contrasts HBV- versus HCV-linked regulation, and evaluates failed anti-miR-122 therapeutic translation, concluding miR-122 is informative yet therapeutically challenging.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Key messages

Introduction

Metabolic dysfunction-associated liver disease progression

Chronic hepatitis leading to HCC

Role of microRNAs and miR-122 in liver pathology

Scope and aims of the review

Journal of Molecular Medicine (2026) 104:110 [https://doi.org/10.1007/s00109-026-02718-1](https://doi.org/10.1007/s00109-026-02718-1) ORIGINAL ARTICLE MicroRNA-122 as a regulator and biomarker of liver disease Sara Ahmadova1,2 · Zofia Wicik1,3 · Joanna Mucha1,4 · Jeff Palatini5 · Katarzyna Ziętal1 · Dagmara Mirowska-Guzel1 · Adam Przybylkowski6 · Ceren Eyileten1,7 Received: 8 January 2026 / Revised: 14 July 2026 / Accepted: 3 August 2026 © The Author(s) 2026 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. Key messages ● Master Liver Regulator: miR-122 is the most abundant liver-specific miRNA, essential for regulating metabolism, inflammation, and cell integrity. Its disruption is a central event in diseases like MAFLD, viral hepatitis, and liver cancer. ● Sensitive Injury Gauge: Circulating miR-122 is a sensitive, non-invasive biomarker that directly reflects hepatocyte damage, outperforming traditional enzymes in tracking liver injury severity. ● Viral Infection Paradox: miR-122 plays opposing roles in viral hepatitis: it is essential for HCV replication but acts asan antiviral tumor suppressor in HBV, where its loss promotes cancer. ● Cancer Driver & Guardian: In hepatocellular carcinoma (HCC), loss of miR-122 is a key event driving tumor growth and metastasis. Its expression patterns differ between HBV-driven and HCV/MASLD-driven cancers. ● Therapeutic Crossroads: While inhibition of miR-122 successfully treated HCV, long-term safety concerns halted development. Current focus has shifted to exploring its restoration as a therapy for MASLD and HBV-related HCC, though delivery remains a challenge. Keywords MiR-122 · Metabolic dysfunction-associated fatty liver disease (MAFLD) · Metabolic dysfunction-associated steatohepatitis (MASH) · Hepatitis B virus (HBV) · Hepatitis C virus (HCV) · Hepatocellular carcinoma (HCC) · Biomarker · Fibrosis · Lipid metabolism · Therapeutic target Extended author information available on the last page of the article Introduction Metabolic dysfunction-associated fatty liver disease (MAFLD), a prevalent condition affecting 25–30% of the global population, progresses from hepatic steatosis to metabolic dysfunction-associated steatohepatitis (MASH),

FAQs

Why is miR-122 considered a central regulator in liver disease?

miR-122 is the most abundant liver-specific microRNA and coordinates multiple processes including lipid metabolism, inflammation, fibrosis, viral replication, and hepatocarcinogenesis.

How does miR-122 behave differently in tissue versus blood when disease progresses?

Hepatic miR-122 expression declines with disease progression, while circulating levels rise with hepatocyte injury, making specimen source and stage essential for biomarker interpretation.

What are the key differences in miR-122 regulation between HBV- and HCV-associated disease?

The review contrasts etiology-specific regulation in which epigenetic silencing and interferon-linked mechanisms lead to divergent miR-122 expression patterns in HBV versus HCV contexts.

Sep 22, 2026

Uploaded by moss~