Abstract
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.
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Data availability
The data generated and analyzed in this study were available.
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Funding
This study was supported by Major Science and Technology Project of Gansu Province (20ZD7FA003, 22ZD6FA050, 22JR9KA002); The Fundermental Research Funds for the Central Universities (lzujbky-2021-ct18); The Natural Science Foundation of Gansu Province under Grant (No. 20JR10RA732); The Science and Technology Program of Gansu province (No. 23JRRA1015); Fundamental Research Funds for the Central Universities (lzujbky-2022-sp08); Medical Innovation and Development Project of Lanzhou University (lzuyxcx-2022-154, lzuyxcx-2022-141), and Gansu Province Health Industry Scientific Research Project (GSWSKY-2019-66).
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Conceptualization, WH and YL; writing—original draft preparation, CH; writing—review and editing, XZ, YG, DW, FT, BZ, TL and WH; visualization, CH. All the authors have read and agreed to the published version of the manuscript.
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This study was approved by the Ethics committee of Lanzhou University Second Hospital (2021A-153 and D2021-136).
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Huo, C., Gu, Y., Wang, D. et al. STAT1 suppresses the transcriptional activity of TRIM21 in gastric cancer. J Cancer Res Clin Oncol 149, 15335–15348 (2023). https://doi.org/10.1007/s00432-023-05307-8
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DOI: https://doi.org/10.1007/s00432-023-05307-8