# DEPDC7 as a potential tumor suppressor in hepatocellular carcinoma: preliminary evidence for targeting the JAK1/STAT3 axis

## TL;DR

This study shows that DEPDC7, a liver-specific protein, acts as a tumor suppressor in liver cancer by inhibiting cell growth and migration.

## Contribution

The study provides preliminary evidence that DEPDC7 suppresses HCC by targeting the JAK1/STAT3 signaling pathway.

## Key findings

- DEPDC7 overexpression inhibits cell proliferation and migration in HCC cells.
- DEPDC7 suppresses the JAK1/STAT3 pathway and epithelial–mesenchymal transition.
- DEPDC7 promotes cell cycle arrest and apoptosis in hepatocellular carcinoma.

## Abstract

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 pathway was 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.