What question did this study set out to answer?

This research aims to investigate the role of miR-26a-5p in metabolic liver disease progression and its linkage to hepatocellular carcinoma.

April 24, 2026Frontiers in Cell and Developmental Biology0 citationsOpen Access

Integrative transcriptomic analysis reveals miR-26a-5p downregulation and a potential predictive gene signature for the progression of metabolic liver disease

ASAndrei Sorop AGAlina-Veronica GhionescuInstitutul Clinic Fundeni DADiana Larisa AncuțaInstitutul Clinic Fundeni

Key Points

This research aims to investigate the role of miR-26a-5p in metabolic liver disease progression and its linkage to hepatocellular carcinoma.
Quantified hepatic miR-26a-5p expression in C57BL/6 mice on a high-carbohydrate diet.
Analyzed public transcriptomic datasets to identify downstream candidates associated with MASLD and HCC.
Examined associations with tumor features and evaluated protein expression after miR-26a-5p modulation.
Identified miR-26a-5p as a candidate prognostic indicator for metabolic liver disease progression.
Confirmed suppressed miR-26a-5p expression as a hallmark of diet-induced metabolic changes.
Constructed a transcriptional signature that effectively stratifies MASLD patients at risk for progression to HCC.

Abstract

Background Metabolic dysfunction–associated steatotic liver disease (MASLD) is an important inducer of hepatocellular carcinoma (HCC). MicroRNAs are key regulators of tumorigenesis. Among these, miR-26a-5p is known to be associated with liver pathogenesis, yet its role in linking MASLD progression to HCC development remains incompletely understood. Methods Hepatic miR-26a-5p expression was quantified in the C57BL/6 mice with a 3-month high-carbohydrate diet (HCD). Public transcriptomic datasets with MASLD and HCC samples were analyzed to identify predicted miR-26a-5p downstream candidates upregulated in the above-mentioned diseases. Associations with tumor features were examined, and protein expression of β-catenin, c-MYC and EpCAM were evaluated after miR-26a-5p modulation. Results Integrative bioinformatics identified miR-26a-5p as a candidate prognostic indicator for metabolic liver disease progression. In vivo , results confirmed that suppressed miR-26a-5p expression is a hallmark of diet-induced metabolic perturbation. Mechanistically, in vitro modulation of miR-26a-5p attenuated oncogenic signaling via the β-catenin/c-Myc/EpCAM axis, establishing its role as a tumor suppressor. Notably, in silico analysis of HCC tissues revealed that high miR-26a-5p levels correlate with enhanced antitumor immunity. Leveraging these insights, we constructed a transcriptional signature from miR-26a-5p downstream candidates and MASLD-HCC differentially expressed genes. This signature effectively stratifies MASLDpatients, discriminating molecular risk groups associated with progression to HCC. Conclusion Integrating transcriptomic, clinical and experimental data suggests the role of miR-26a-5p, along with the MASLD-HCC gene signature (EpCAM, DTNA, and KPNA2), may serve as an early molecular indicator and mechanistic modulator of hepatocarcinogenesis, warranting further functional investigation.

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