A Review of Liver Cancer Development Driven by the AP-1/c-Jun~Fra-2 Dimer through c-Myc

Song Liu; Jinhuan Liu

doi:10.54254/2753-8818/2025.AU27720

Abstract

Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related mortality worldwide. Recent epidemiological data demonstrate a rising incidence of HCC, which is further compounded by its insidious onset, poor prognosis, and limited therapeutic options. Elucidating its molecular pathogenesis and identifying viable therapeutic targets remain critical unmet needs. While prior studies have implicated members of the AP-1 (Activator Protein-1) transcription factor family (e.g., c-Fos and c-Jun) in hepatocarcinogenesis, the roles of Fos-related antigens (Fra-1 and Fra-2) remain poorly characterized. This study investigates the mechanistic interplay between c-Jun/Fra-2 heterodimers and the oncogenic driver c-Myc—a well-established molecular nexus in HCC pathogenesis—unraveling their collective impact on HCC proliferation, inflammatory cascades, and tumorigenesis. Through a systematic literature review, this study delineates the pro-tumorigenic role of the c-Jun/Fra-2-Myc axis in murine HCC models. This paper elucidates how c-Jun-Fra-2 heterodimers transcriptionally regulate c-Myc to orchestrate core oncogenic programs. Integrative analysis of the HCC tumor microenvironment (TME) further reveals that c-Jun-Fra-2 overexpression induces TME remodeling, characterized by low-grade inflammation, mild fibrosis, and dyslipidemia—key permissive factors for HCC progression. The findings underscore the pivotal role of c-Jun-Fra-2 heterodimers in HCC pathogenesis, wherein their upregulation of c-Myc drives tumor initiation and progression. Notably, the c-Jun-Fra-2/c-Myc axis exhibits both reversibility and dependency, suggesting a therapeutic vulnerability. In HCC patients with elevated c-Jun-Fra-2 expression, pharmacological inhibition using the BET inhibitor JQ-1 significantly attenuates tumor growth, highlighting its potential as a precision therapy target. This work advances the molecular understanding of HCC and provides a rationale for targeted intervention in defined subsets.

Keywords: AP-1 , c-Jun/Fra-2 , HCC , c-Myc

Article Information

Received: 1 October 2025

Published: 14 October 2025

DOI: https://doi.org/10.54254/2753-8818/2025.AU27720

Article Type: Research Article

Cite this article

Liu,S.;Liu,J. (2025). A Review of Liver Cancer Development Driven by the AP-1/c-Jun~Fra-2 Dimer through c-Myc. Theoretical and Natural Science,141,86-92.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

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About this Volume

Volume Title: TNS Vol.141

Part of Series: Theoretical and Natural Science

ISSN: 2753-8818 (Print) / 2753-8826 (Online)

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