The GDF11 represses the Stat3 signaling pathway, conferring metabolic, inflammatory, and oncogenic restrictions in cells derived from human hepatocellular carcinoma.
Introduction and Objectives: GDF11 has shown potential in displaying anti-tumor effects in cells derived from human HCC, but the molecular mechanisms that lead to this, as well as the early transcriptomic response of GDF11 in HCC, remain a mystery. To identify potential targets for therapeutic inter...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-04-01
|
| Series: | Annals of Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268125000171 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Introduction and Objectives: GDF11 has shown potential in displaying anti-tumor effects in cells derived from human HCC, but the molecular mechanisms that lead to this, as well as the early transcriptomic response of GDF11 in HCC, remain a mystery. To identify potential targets for therapeutic intervention revealed by GDF11 treatment in HCC. Materials and Patients: Huh7 cells were treated for 12 h with 50 ng/ml of GDF11, and sequencing was performed using the Illumina HiSeq4000 platform. The results were filtered with a p≤0.01, ± 1.5-fold change, and an FDR= 0.05. Functional and enrichment analysis was done using the Ingenuity Pathway Analysis (IPA) program. Results: Our data show 1450 differentially expressed genes. It is observed that GDF11 has a profound impact on highly oncogenic pathways, highlighting the Stat3 pathway, beta-catenin, and HIF-1 alpha, among others. Functional analysis revealed that GDF11 could reduce cholesterol and lipid metabolism in general, inflammation, drug resistance, and stemness capacity. It is noteworthy that tumors grown under a lipid-rich environment exhibit significant activation of Stat3, so the decrease in the molecular signature of Stat3 induced by GDF11 strongly suggests a mechanism mediated by the repression of the pathway of this factor transcription, impacting metabolism, inflammation, differentiation, and drug resistance. Conclusions: Our study's novel finding is that GDF11 represses the Stat3 signaling pathway, thereby imposing metabolic, inflammatory, and oncogenic restrictions. GDF11 represents a good promise in the treatment of HCC. |
|---|---|
| ISSN: | 1665-2681 |