ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Cell Signaling
This article is part of the Research TopicHarnessing Immune Microenvironment Reprogramming in Hepatocellular Carcinoma: Mechanisms and Therapeutic InnovationView all articles
DEPDC7 as a Potential Tumor Suppressor in Hepatocellular Carcinoma: Preliminary Evidence for Targeting the JAK1/STAT3 Axis
Provisionally accepted
Changhao Bao
Zhijun Liao*
Jiaqi WangGenwang ChenSisi GongJiewei HuangJie LiuRuiyang HuangQilong Pan
Chunmei Fan*- Fujian Medical University, Fuzhou, China
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Hepatocellular carcinoma (HCC) progression involves disruption of oncogenic and tumor-suppressive signaling networks. DEPDC7 (DEP domain-containing protein 7), a liver-specific gene associated with intercellular communication, is highly expressed in normal hepatocytes but markedly downregulated in HCC. Here, we investigated the tumor-suppressive mechanisms of DEPDC7 using Huh-7 cells. Structural analysis revealed conserved DEP and RhoGAP domains, with multiple predicted post-translational modification sites suggesting regulatory potential. DEPDC7 expression was significantly reduced in HCC cells and localized to both cytoplasm and nucleus. Functionally, DEPDC7 overexpression inhibited cell proliferation and migration. RNA-seq analysis identified the JAK1/STAT3 pathwaywas the most suppressed upon DEPDC7 overexpression, with downregulation of JAK1 and STAT3. Molecular docking and co-immunoprecipitation confirmed direct interaction between DEPDC7 and the JAK1 kinase domain, indicating regulation through physical binding. Moreover, DEPDC7 overexpression suppressed epithelial–mesenchymal transition (EMT), increasing E-cadherin while reducing N-cadherin and vimentin. Morphological changes observed by scanning electron microscopy supported reduced migratory capacity. Collectively, DEPDC7 exerts tumor-suppressive effects by (1) promoting cell cycle arrest and apoptosis, (2) inhibiting JAK1/STAT3 signaling, and (3) attenuating EMT. These findings provide mechanistic evidence that DEPDC7 functions as a tumor suppressor in HCC, highlighting its potential as a therapeutic target.
Keywords: DEPDC7, EMT, Hepatocellular Carcinoma, JAK1/STAT3, RNA-Seq
Received: 06 Oct 2025; Accepted: 22 Jan 2026.
Copyright: © 2026 Bao, Liao, Wang, Chen, Gong, Huang, Liu, Huang, Pan and Fan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhijun Liao
Chunmei Fan
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