Huo Chengdong, Gu Yanmei, Wang Daijun, Zhang Xiaoxia, Tang Futian, Zhao Bin, Liu Tao, He Wenting, Li Yumin
Department of the Second Clinical Medical College, Lanzhou University, Lanzhou, 730030, China.
Department of Ophthalmology, Lanzhou University Second Hospital, Lanzhou, 730030, China.
J Cancer Res Clin Oncol. 2023 Nov;149(17):15335-15348. doi: 10.1007/s00432-023-05307-8. Epub 2023 Aug 28.
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.
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.
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.
TRIM21 is a tumor-suppressive gene in gastric cancer, and its transcriptional activity is inhibited by STAT1.
含三联基序蛋白21（TRIM21）具有E3泛素连接酶活性，参与体内多种生物学过程的调控。已发现TRIM21与多种癌症密切相关。然而，其在胃癌中的作用尚不清楚。
利用加权基因共表达网络分析（WGCNA）和蛋白质-蛋白质相互作用（PPI）分析筛选TCGA数据库以获取TRIM21。使用TCGA数据库评估TRIM21表达与患者临床特征、预后、功能富集和免疫细胞浸润的相关性。通过体内和体外实验验证TRIM21在细胞增殖、凋亡和侵袭中的作用。利用UCSC和JASPAR数据库评估信号转导和转录激活因子1（STAT1）对TRIM21转录的调控作用。最后，采用双荧光素酶报告基因实验证实STAT1对TRIM21转录活性的调控。
作为关键基因，TRIM21的高表达抑制胃癌生长，且在凋亡、细胞增殖和JAK/STAT信号通路中显著富集。TRIM21表达与多种肿瘤浸润性细胞（TICs）呈正相关，包括T细胞、自然杀伤细胞和树突状细胞。在体内实验中，TRIM21抑制胃癌细胞系的功能，包括抑制增殖和迁移以及促进凋亡。数据库分析和双荧光素酶报告基因实验表明，STAT1抑制TRIM21的转录活性。体内实验证实TRIM21抑制肿瘤生长，且STAT1表达与TRIM21呈负相关。
TRIM21是胃癌中的一个肿瘤抑制基因，其转录活性受STAT1抑制。
