TRIM37 Promotes Pancreatic Cancer Progression through Modulation of Cell Growth, Migration, Invasion, and Tumor Immune Microenvironment

Thi, Tuyen; Yeh, Chun-Chieh; Wu, Guowei; Hsu, Chia‐Chen; Chang, Hung-Chih; Chen, Hui-Chen

doi:10.3390/ijms23031176

Cited by 6 publications

(3 citation statements)

References 45 publications

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“…Recently, a growing body of studies has demonstrated how E3 ligases function in the tumor microenvironment ( Do et al, 2022 ; Hosein et al, 2022 ; Iwamoto et al, 2022 ). The tumor microenvironment consists of different cells, including tumor cells, tumor stem cells, and stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas

et al. 2022

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Gliomas, a type of primary brain tumor, have emerged as a threat to global mortality due to their high heterogeneity and mortality. A low-grade glioma (LGG), although less aggressive compared with glioblastoma, still exhibits high recurrence and malignant progression. Ubiquitination is one of the most important posttranslational modifications that contribute to carcinogenesis and cancer recurrence. E3-related genes (E3RGs) play essential roles in the process of ubiquitination. Yet, the biological function and clinical significance of E3RGs in LGGs need further exploration. In this study, differentially expressed genes (DEGs) were screened by three differential expression analyses of LGG samples from The Cancer Genome Atlas (TCGA) database. DEGs with prognostic significance were selected by the univariate Cox regression analysis and log-rank statistical test. The LASSO-COX method was performed to identify an E3-related prognostic signature consisting of seven genes AURKA, PCGF2, MAP3K1, TRIM34, PRKN, TLE3, and TRIM17. The Chinese Glioma Genome Atlas (CGGA) dataset was used as the validation cohort. Kaplan–Meier survival analysis showed that LGG patients in the low-risk group had significantly higher overall survival time than those in the high-risk group in both TCGA and CGGA cohorts. Furthermore, multivariate Cox regression analysis revealed that the E3RG signature could be used as an independent prognostic factor. A nomogram based on the E3RG signature was then established and provided the prediction of the 1-, 3-, and 5-year survival probability of patients with LGGs. Moreover, DEGs were analyzed based on the risk signature, on which function analyses were performed. GO and KEGG analyses uncovered gene enrichment in extracellular matrix–related functions and immune-related biological processes in the high-risk group. GSEA revealed high enrichment in pathways that promote tumorigenesis and progression in the high-risk group. Furthermore, ESTIMATE algorithm analysis showed a significant difference in immune and stroma activity between high- and low-risk groups. Positive correlations between the risk signature and the tumor microenvironment immune cell infiltration and immune checkpoint molecules were also observed, implying that patients with the high-risk score may have better responses to immunotherapy. Overall, our findings might provide potential diagnostic and prognostic markers for LGG patients and offer meaningful insight for individualized treatment.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas

et al. 2022

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“…In addition, chronic inflammation in the TME can activate multiple inflammatory pathways in tumor cells, tumor stromal cells, and ICCs, thereby promoting the release of inflammatory mediators, including growth factors, cytokines, chemokines, and proangiogenic factors [ 190 , 191 ]. The ubiquitin ligases Cop1, TRIM37, and UBR5 have been shown to modulate the production of key chemokines and cytokines in tumor cells to promote the recruitment and activation of immunosuppressive macrophages [ 192 – 194 ]. Downregulation of the deubiquitinase USP12 in lung cancer cells promotes the hyperactivation of NF-κB, a positive regulator of inflammation, and generates a tumor-promoting secretome by reducing the stability of PPM1B [ 195 ].…”

Section: Introductionmentioning

confidence: 99%

Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy

Zhao

et al. 2023

Exp Hematol Oncol

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Tumor development relies on a complex and aberrant tissue environment in which cancer cells receive the necessary nutrients for growth, survive through immune escape, and acquire mesenchymal properties that mediate invasion and metastasis. Stromal cells and soluble mediators in the tumor microenvironment (TME) exhibit characteristic anti-inflammatory and protumorigenic activities. Ubiquitination, which is an essential and reversible posttranscriptional modification, plays a vital role in modulating the stability, activity and localization of modified proteins through an enzymatic cascade. This review was motivated by accumulating evidence that a series of E3 ligases and deubiquitinases (DUBs) finely target multiple signaling pathways, transcription factors and key enzymes to govern the functions of almost all components of the TME. In this review, we systematically summarize the key substrate proteins involved in the formation of the TME and the E3 ligases and DUBs that recognize these proteins. In addition, several promising techniques for targeted protein degradation by hijacking the intracellular E3 ubiquitin-ligase machinery are introduced.

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“…Trim37, a member of the Tripartite motif-containing (TRIM) superfamily [7], is characterized by three structural domains: RING nger, B-box, and coiled-coil [8]. A growing body of evidence suggests that TRIM37 is an oncogene upregulated in multiple malignancies, including pancreatic cancer [9], ovarian cancer [10], colorectal cancer, gastric cancer [11] and non-small cell lung cancer, involved in the regulation of promoting proliferation, epithelial-mesenchymal transition and apoptosis for tumor cells [12]. Previous reports revealed that TRIM37 harbored ubiquitin E3 ligase, which could regulate protein stability [13].…”

Section: Introductionmentioning

confidence: 99%

N6-methyladenosine-modified TRIM37 augments sunitinib resistance by promoting the ubiquitin-degradation of SmARCC2 via activating the Wnt signaling pathway in renal cell carcinoma

Luo,

Dai,

Dong

et al. 2023

Preprint

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Tripartite motif-containing 37 (TRIM37) is reportedly a key member of the superfamily of TRIM proteins. Emerging evidence underscores the close association between dysregulated TRIM37 expression and the progression of various human malignancies. However, the precise biological functions and regulatory mechanisms of TRIM37 remain elusive. This study aimed to elucidate the impact of TRIM37 on the chemotherapy sensitivity of renal cell carcinoma (RCC) and uncover its specific molecular regulatory role. Using RT-qPCR and western blot assays, we assessed TRIM37 expression in both RCC patients and RCC cells. Through in vitro and in vivo experiments, we investigated the effects of TRIM37 silencing and overexpression on RCC cell proliferation, stemness capacity, and chemotherapy sensitivity using colony formation and sphere formation assays. Additionally, a co-immunoprecipitation (Co-IP) experiment was conducted to explore putative interacting proteins. Our results revealed elevated TRIM37 expression in both RCC patient tumor tissues and RCC cells. Functional experiments consistently demonstrated that TRIM37 silencing reduced proliferation and stemness capacity while enhancing chemotherapy sensitivity in RCC cells. Furthermore, we discovered that TRIM37 mediates the degradation of SMARCC2 via ubiquitin-proteasome pathways by activating the Wnt signaling pathway. In conclusion, this study not only sheds light on the biological role of TRIM37 in RCC progression but also identifies a potential molecular target for therapeutic intervention in RCC patients.

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TRIM37 Promotes Pancreatic Cancer Progression through Modulation of Cell Growth, Migration, Invasion, and Tumor Immune Microenvironment

Cited by 6 publications

References 45 publications

Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas

Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas

Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy

N6-methyladenosine-modified TRIM37 augments sunitinib resistance by promoting the ubiquitin-degradation of SmARCC2 via activating the Wnt signaling pathway in renal cell carcinoma

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