TRIM21 deficiency promotes cell proliferation and tumorigenesis via regulating p21 expression in ovarian cancer

Sun, Jesse; Chen, Xintian; Ji, Xiaofan; Meng, Sen; Wang, Wenwen; Wang, Pengfei; Bai, Jing; Li, Zhongwei; Chen, Youguo

doi:10.1080/21655979.2022.2042134

Cited by 11 publications

(9 citation statements)

References 29 publications

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“…Our comparison of TRIM21 expression in different tissue types revealed a significantly higher level of TRIM21 expression in PTs compared with LMs. In ovarian, renal, and hepatocellular carcinoma, TRIM21 overexpression inhibits cell migration in vitro and in vivo [ 18 , 19 , 20 ]. Nevertheless, we did not observe significant differences in the TRIM21 expression of PTs in terms of the occurrence of LMs.…”

Section: Discussionmentioning

confidence: 99%

“…The role of TRIM21 as a prognostic biomarker has previously been analyzed in other cancer entities. For example, decreased TRIM21 expression in ovarian cancer, diffuse large cell lymphoma, and breast cancer is associated with shorter OS rates [ 18 , 24 , 25 ]. In thyroid cancer, higher TRIM21 expression is correlated with an increased risk of recurrences and lymph node metastases [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…To assess the HPV status in the tumor samples, we used the p16 status as a surrogate marker [ 9 ]. Protein expression was detected with immunohistochemical staining using the mouse monoclonal antibody p16 (p16 CINtec ready to use kit, clone E6H4™, Roche Ventana Medical Systems, Tucson, AZ, USA), as described previously [ 18 , 38 ]. Binding was revealed using the Dab system delineated above.…”

Section: Methodsmentioning

confidence: 99%

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TRIM21 Expression as a Prognostic Biomarker for Progression-Free Survival in HNSCC

Bernuth

Ribbat‐Idel

Klapper

et al. 2023

IJMS

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Patients with head and neck squamous cell carcinoma (HNSCC) continue to have a rather poor prognosis. Treatment-related comorbidities have negative impacts on their quality of life. TRIM21 is a cytosolic E3 ubiquitin ligase that was initially described as an autoantigen in autoimmune diseases and later associated with the intracellular antiviral response. Here, we investigated the role of TRIM21 as a biomarker candidate for HNSCC in predicting tumor progression and patient survival. We analyzed TRIM21 expression and its association with clinical-pathological parameters in our HNSCC cohort using immunohistochemistry. Our HNSCC cohort included samples from 419 patients consisting of primary tumors (n = 337), lymph node metastases (n = 156), recurrent tumors (n = 54) and distant metastases (n = 16). We found that cytoplasmic TRIM21 expression was associated with the infiltration of immune cells into primary tumors. In addition, TRIM21 expression was significantly higher in primary tumors than in lymph node metastases, and increased TRIM21 expression was correlated with shorter progression-free survival in HNSCC patients. These results suggest that TRIM21 could be a new biomarker for progression-free survival.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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TRIM21 Expression as a Prognostic Biomarker for Progression-Free Survival in HNSCC

Bernuth

Ribbat‐Idel

Klapper

et al. 2023

IJMS

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“…This may be related to the mechanism of TRIM21 , a target of miR-6529a, which promotes glioma cell growth and suppresses cell senescence through the p53-p21 pathway [ 29 ]; however, the specific mechanism requires further verification. TRIM21 can control the process of ubiquitination and degradation of FASN to regulate lipid metabolism [ 30 ], negatively regulate the crosstalk between the PI3K/AKT pathway and PPP metabolism [ 31 ], and affect cell apoptosis and proliferation [ 32 ]. Cell proliferation is influenced by a variety of cell cycle regulators [ 33 ], and our sequencing data showed that lncFAM200B overexpression in preadipocytes decreased the expression levels of cell cycle-related genes ( Figure 1 B), including CCNA2 , BUB1 , KIF20A , and TOP2A .…”

Section: Discussionmentioning

confidence: 99%

Molecular Regulation of Yak Preadipocyte Differentiation and Proliferation by LncFAM200B and ceRNA Regulatory Network Analysis

Ran

Yang

Luo

et al. 2022

Cells

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The positive regulatory role of lncFAM200B in differentiation and lipid deposition in yak intramuscular preadipocytes has been demonstrated in our previous study. However, the regulatory mechanisms remain unclear. In this study, we aimed to produce complete mRNA and microRNA (miRNA) profiles after adenovirus-mediated lncFAM200B overexpression in yak preadipocytes using high-throughput sequencing. We constructed a competing endogenous RNA (ceRNA) network with lncFAM200B as the core and identified the functions of the selected target miRNA during cell proliferation and differentiation. We obtained 118 differentially expressed genes (DEGs) after lncFAM200B overexpression, 76 of which were up-regulated, including Notch signaling members NOTCH3, DTX3L, and HES4, and 42 DEGs were down-regulated, including genes related to the cell cycle (CCNA2, BUB1, CDC20, TOP2A, and KIF20A). Additionally, many ubiquitin-mediated proteolysis pathway members were also significantly up-regulated (BUA7, PML, TRIM21, and TRIM25). MiRNA sequencing showed that 13 miRNAs were significantly up-regulated, and 12 miRNAs were down-regulated. Among them, 29 targets of 10 differentially expressed miRNAs (DEMs) were differentially expressed, including miR-152-FBXO33, miR-6529a-TRIM21, miR-148c-NOTCH3, and the miR-6529b-HES4 axis. We further verified that overexpression and inhibition of miR-6529a can inhibit and promote, respectively, the proliferation and differentiation of preadipocytes. Taken together, our study not only revealed the regulatory network of lncFAM200B during yak preadipocytes differentiation but also laid a foundation for elucidating the cause for lower intramuscular fat content in yaks at the molecular level.

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“…TRIM21 belongs to the tripartite motif-containing protein (TRIM) family, and proteins in that family are characterized by a RING domain, B-box domain, coiled-coil domain (CC), and PRY/SPRY region, and have E3 ubiquitin ligase activity [ 4 ]. Some key molecules involved in metabolism pathways have also been defined as substrates of TRIM21 [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability

Chen

Yong

Chen

et al. 2023

J Exp Clin Cancer Res

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Background Metabolic reprogramming is a hallmark of various cancers. Targeting metabolic processes is a very attractive treatment for cancer. Renal cell carcinoma (RCC) is a type of metabolic disease, and the lipidomic profile of RCC is significantly altered compared with that of healthy tissue. However, the molecular mechanism underlying lipid metabolism regulation in RCC is not clear. Methods The XF long-chain fatty acid oxidative stress test kits were used to assess the dependence on long-chain fatty acids and mitochondrial function after knockdown TRIM21 in RCC cells. The effect of TRIM21 on the lipid content in RCC cells was determined by metabolomics analysis, Oil Red O staining, and cellular Nile red staining. qRT-PCR and western blot were used to explore the relationship between TRIM21 and lipogenesis, and then the key molecule sterol regulatory element binding transcription factor 1 (SREBF1) was identified to interact with TRIM21 by immunoprecipitation, which was also identified in an orthotopic model. Subsequently, the relevance and clinical significance of TRIM21 and SREBF1 were analyzed by The Cancer Genome Atlas (TCGA) database, and 239 tissues were collected from RCC patients. Results TRIM21 silencing attenuated the dependence of RCC cells on fatty acids, and enhanced lipid accumulation in RCC cells. TRIM21 overexpression significantly decreased lipid contents by decreasing the expression of lipogenic enzymes via ubiquitination-mediated degradation of SREBF1. SREBF1 is critical for TRIM21-mediated lipogenesis inhibition in vitro and in vivo. Moreover, TRIM21 expression is negatively correlated with SREBF1 expression, and TRIM21-SREBF1 is a reliable combinational biomarker for RCC prognosis. Conclusion The findings from this study reveal a novel pathway through which TRIM21 inhibits the lipid metabolism process of RCC and shed light on the development of targeted metabolic treatment and prognosis diagnosis of RCC.

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TRIM21 deficiency promotes cell proliferation and tumorigenesis via regulating p21 expression in ovarian cancer

Cited by 11 publications

References 29 publications

TRIM21 Expression as a Prognostic Biomarker for Progression-Free Survival in HNSCC

TRIM21 Expression as a Prognostic Biomarker for Progression-Free Survival in HNSCC

Molecular Regulation of Yak Preadipocyte Differentiation and Proliferation by LncFAM200B and ceRNA Regulatory Network Analysis

TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability

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