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STAT1 suppresses the transcriptional activity of TRIM21 in gastric cancer
Chengdong Huo1,2, Yanmei Gu1, Daijun Wang1
1Department of the Second Clinical Medical College, Lanzhou University, Lanzhou, 730030, China.
Purpose:
Tripartite motif-containing protein 21 (TRIM21) has E3 ubiquitin ligase activity and is involved in the regulation of various biological processes in vivo. TRIM21 has been found to have strong associations with various cancers. However, its role in gastric cancer is unclear.
Methods:
The TCGA database was screened to obtain TRIM21 using WGCNA and PPI analyses. The TCGA database was used to evaluate the correlation of TRIM21 expression with patients' clinical characteristics, prognosis, functional enrichment and immune cell infiltration. The role of TRIM21 in cell proliferation, apoptosis and invasion was verified by in vivo and in vitro assays. The UCSC and JASPAR databases were used to evaluate the regulatory role of STAT1 on TRIM21 transcription. Finally, dual-luciferase reporter assay was used to confirm the regulation of TRIM21 transcriptional activity by STAT1.
Results:
As a key gene, high expression of TRIM21 inhibited the gastric cancer growth and was significantly enriched in apoptosis, cell proliferation, and JAK/STAT signaling pathways. TRIM21 expression was positively correlated with a variety of TICs, including T cells, NK cells, and DCs. In vivo assays, TRIM21 inhibited functions in gastric cancer cell lines, including inhibition of proliferation and migration, and promotion of apoptosis. Database analysis and dual-luciferase reporter assay showed that STAT1 inhibited the transcriptional activity of TRIM21. In vivo assays confirmed that TRIM21 inhibited tumor growth, and STAT1 expression was negatively correlated with STAT1.
Conclusion:
TRIM21 is a tumor-suppressive gene in gastric cancer, and its transcriptional activity is inhibited by STAT1.
Insights
Tripartite motif-containing protein 21 (TRIM21) acts as a tumor suppressor in gastric cancer by inhibiting growth and promoting apoptosis. STAT1 negatively regulates TRIM21 transcription, impacting its tumor-suppressive function.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tripartite motif-containing protein 21 (TRIM21) possesses E3 ubiquitin ligase activity and influences diverse biological processes.
- TRIM21 is implicated in various cancers, but its specific role in gastric cancer remains largely uncharacterized.
Purpose of the Study:
- To elucidate the function of TRIM21 in gastric cancer.
- To investigate the regulatory mechanisms controlling TRIM21 expression and activity in gastric cancer.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for gene expression analysis (WGCNA, PPI).
- Performed in vivo and in vitro assays to assess TRIM21's impact on cell proliferation, apoptosis, and invasion.
- Employed bioinformatics databases (UCSC, JASPAR) and dual-luciferase reporter assays to determine STAT1's regulatory role on TRIM21 transcription.
Main Results:
- High TRIM21 expression correlated with inhibited gastric cancer growth, enriched apoptosis, and JAK/STAT signaling pathways.
- TRIM21 expression positively associated with tumor-infiltrating cells (TICs), including T cells, NK cells, and DCs.
- TRIM21 suppressed gastric cancer cell proliferation and migration while promoting apoptosis; STAT1 was found to inhibit TRIM21 transcriptional activity.
Conclusions:
- TRIM21 functions as a tumor-suppressive gene in gastric cancer.
- STAT1 negatively regulates the transcriptional activity of TRIM21, thereby influencing its tumor-suppressive role.
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