TRIM proteins in blood cancers

Ding

et al. 2020

Preprint

Abstract Background Emerging evidence shows that the deregulation of tripartite motif (TRIM) family proteins have various functions in cellular processes and play important role in innate immunity, nervous system diseases, protein quality control and carcinogenesis. However, the precise biological function and molecular mechanism of TRIM family proteins in ovarian cancer chemo-resistance remain unclear. Methods The protein and mRNA expression of TRIM37 in ovarian cancer cell lines and patient tissues were determined using Real-time PCR and Western blot and IHC respectively. Functional assays, such as MTT, FACS, and Tunel assay used to determine the oncogenic role of TRIM37 in human ovarian cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM37 promotes chemoresistance in ovarian cancer cells. Results Herein, we found that the protein and mRNA expression of TRIM37 were markedly overexpressed in ovarian cancer tissues which shown partially responded to cisplatin chemotherapy. Moreover, TRIM37 expression was inversely correlated with patient survival in our cohort HCC tissue samples and public HCC database. Overexpression of TRIM37 confers cisplatin resistance on ovarian cancer cells; but, inhibition of TRIM37 sensitized ovarian cancer cell lines to cisplatin cytotoxicity both in vitro and in vivo. Additionally, TRIM37 upregulated the levels of nuclear β-catenin, thereby activating canonical wnt/β-catenin signaling. Conclusions our results demonstrate that targeting TRIM37/β-catenin axis may represent a promising strategy to enhance cisplatin response in patients with chemo-resistant ovarian cancer.

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Tripartite Motif Containing 37 Activates the Wnt/β-catenin Signalling Pathway and Confers Cisplatin Resistance to Ovarian Carcinoma

Ding

et al. 2020

Preprint

“…Tripartite motif (TRIM) proteins were the member of the RING family of E3 ubiquitin ligase, including RING-finger domain, Zinc-binding domain (B-boxes domain), Coiled-coil domain, and C-terminal domain, and the presence of RING finger indicated that TRIM protein as E3 participated in various physiological processes in cells [10][11][12][13]. Previous studies had reported the important functions of TRIM proteins in the development of various cancers, which played an important role in cell cycle, apoptosis, differentiation, metabolism, and immune response [14][15][16][17]. The clinical manifestations observed in human diseases caused by TRIM gene mutations might be due to change in TRIM activity during ubiquitination [18,19].…”

Section: Introductionmentioning

confidence: 99%

Tripartite motif containing 35 contributes to the proliferation, migration, and invasion of lung cancer cellsin vitroandin vivo

Zhang

et al. 2020

Bioscience Reports

The tripartite motif (TRIM) family is a family of proteins with highly conserved domains. Previous researches have suggested that the members of TRIM family proteins played a crucial role in cancer development and progression. Our study explored the relationship between TRIM35 and non-small cell lung cancer (NSCLC). The study showed that the expression of TRIM35 was increased in NSCLC samples, and patients with high expression of TRIM35 had a poor clinical prognosis. Overexpression of TRIM35 in NSCLC cell line H460 promoted cell proliferation, migration, and invasion, knockdown of TRIM35 produced an opposite result in A549 and H1299 cell lines. In vivo study further confirmed that overexpression of TRIM35 promoted tumor formation. The RNA-seq analysis suggested that TRIM35 might promote lung cancer proliferation, migration, and invasion by regulating cancer-associated functions and signaling pathways. Hence, we identified TRIM35 played a significant role in tumoral growth and was a potential diagnosis and prognosis target for lung cancer.

Clinical and Experimental Immunology

“…TRIM21 belongs to the tripartite motif (TRIM) protein family, thus denoted for the RING, B-box and coiled-coil motif common to its members [9,10]. The TRIM proteins function as E3 ligases in the ubiquitination cascade [11,12] and have been implicated as regulators of immunity and cellular processes such as proliferation, differentiation and apoptosis [13][14][15]. TRIM21 is predominantly expressed in haematopoietic cells and has been shown to ubiquitinate multiple interferon regulatory factors (IRFs), proteins of the nuclear factor kappa B (NF-kB) pathway, as well as proteins regulating the cell cycle [12,16,17].…”

Section: Introductionmentioning

confidence: 99%

The Sjögren's syndrome-associated autoantigen Ro52/TRIM21 modulates follicular B cell homeostasis and immunoglobulin production

Brauner

Ivanchenko

Thorlacius

et al. 2018

Systemic rheumatic diseases are characterized by abnormal B cell activation with autoantibody production and hypergammaglobulinaemia. Ro52/SSA, also denoted tripartite motif (TRIM)21, is a major autoantigen in Sjögren's syndrome and systemic lupus erythematosus. Interestingly, TRIM21-deficient mice develop systemic autoimmunity with B cell-driven manifestations such as autoantibodies, hypergammaglobulinaemia and glomerulonephritis following tissue injury. The mechanisms by which TRIM21-deficiency leads to enhanced B cell activation and antibody production are, however, not well understood, and to further elucidate the role of TRIM21 in systemic autoimmunity, we investigated the B cell phenotype and antibody responses of Trim21 mice following immunization with thymus-dependent (TD) and thymus-independent (TI) antigens. We found that TRIM21-deficient mice developed significantly higher specific antibody titres than their wild-type counterparts upon B cell receptor (BCR) engagement by TD and TI type II antigens, and this was accompanied by an altered B cell phenotype. Furthermore, BCR cross-linking, but not anti-CD40 stimulation, in vitro resulted in a significantly higher proliferation of Trim21 cells. We also observed that splenic follicular B cells were expanded not only in immunized mice but also already in young, unmanipulated Trim21 mice, and transcriptomic analysis of these cells revealed an up-regulation of genes associated with B cell differentiation, indicating a role for TRIM21 in their regulation. In conclusion, in this study we describe a link between the rheumatic autoantigen Ro52/TRIM21 and increased antibody production associated with follicular B cell expansion, implicating a potential role for Ro52/TRIM21 in the pathogenesis of systemic autoimmune diseases.