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Background Tripartite motif 47 (TRIM47), a member of the TRIM family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). We found that levels of TRIM47 mRNA and protein were increased significantly in colorectal tumors compared with nontumor tissues and the increased levels were associated with advanced tumor stage and poor outcome. Methods We used quantitative polymerase chain reaction and western blot to measure levels of TRIM47 mRNA and protein in human colorectal cancer and paired normal tissues. TRIM47 was knocked down and overexpressed in colorectal cancer cells, and the effects on cell proliferation, migration and growth of xenograft tumors in nude mice were assessed. The signaling pathways were examined by western blot and immunoprecipitation assays. Results TRIM47 promoted CRC proliferation and metastasis in vitro and in vivo as an oncogene. Mechanistically, TRIM47 interacted physically with SMAD4, increasing its ubiquitination and degradation. Loss of SMAD4 leaded to up-regulation of CCL15 expression and caused growth and invasion in human CRC cells through the CCL15-CCR1 signaling. Moreover, TRIM47 overexpression played a role in CRC chemoresistance in response to 5-FU therapy. Conclusions Our study demonstrated a functional role of the TRIM47-SMAD4-CCL15 axis in CRC progression and suggested a potential target for CRC therapy.

Hypopharyngeal and laryngeal cancers which belong to head and neck squamous cell carcinoma (HNSCC) are the two most malignant types of head and neck cancer, characterized by a low 5‐year survival rate, high recurrence and metastasis rate. It is vital to explore strategies to suppress metastasis and improve prognosis for patients with these cancers. In this research, we analyzed the clinical data and found that E3 ubiquitin ligase TRIM47 was upregulated in cancer tissues of hypopharyngeal cancer and was closely associated with poor survival outcomes. In terms of mechanism, we performed tandem affinity chromatography and denatured Ni‐NTA Agarose pulldown. As a result, TRIM47 was found to interact with vimentin and control vimentin stabilization through ubiquitination, specifically in the form of K63 chains. Importantly, through experiments of cancer cell viability and migration, we found that TRIM47 could enhance the proliferation and metastasis abilities of cancer cells in a vimentin‐dependent manner, thus promoting the advancement of hypopharyngeal and laryngeal cancers. TRIM47 was verified to regulate cancer cells metastasis in vivo using metastasis models. All these results imply that TRIM47 emerges as a potential biomarker for early diagnosis and metastasis prediction of hypopharyngeal and laryngeal cancers and represents a promising therapeutic target. E3 ubiquitin ligase TRIM47 overexpresses in hypopharyngeal cancer and is related to poor prognosis. TRIM47 regulates vimentin which is associated with metastasis with K63‐linked ubiquitination in hypopharyngeal and laryngeal cancers.

Trim47, a TRIM C-VII subgroup protein characterized by a conserved SPRY domain, has been primarily studied for its ubiquitin-dependent roles in mammals. This study reports a paradigm-shifting finding in teleost immunology: grass carp Trim47 (gcTrim47) employs its SPRY domain to execute a novel, ubiquitin-independent antiviral pathway, selectively degrading GCRV-I nonstructural proteins NS38/NS80 via autophagy-mediated clearance. Unlike mammalian TRIMs, gcTrim47 antiviral activity is strictly dependent on its SPRY domain—devoid of RING/B-box domains critical for E3 ligase function—revealing an evolutionarily divergent mechanism where substrate-targeting specificity, not ubiquitination, drives viral replication factory (viral inclusion body, VIB) dismantling. Functional assays demonstrated that gcTrim47 overexpression in CIK cells reduced viral titers and suppressed VIB formation, with SPRY domain deletion ablating these effects. In vivo , a yeast surface-display platform presenting gcTrim47-PYD1 conferred 32.94% relative percent survival (RPS) against GCRV-II infection, the first reported use of a TRIM family protein as an antiviral immunogen in grass carp. This strategy mitigated splenic/kidney viral loads and alleviated histopathological damage, including tubular necrosis and inflammatory infiltration. The successful application of this mechanism into a yeast-based immunization strategy highlights its potential for developing novel antiviral biotherapeutics in aquaculture.

Sevoflurane (SEV), usually causing neuronal damage and cognitive dysfunction, is one of the most commonly used anesthetics in clinical practice. However, the function of Trim47 in SEV-induced neuronal impairment remains elusive. The aim of this study was to study the effect of knocking down Trim47 on the nerve injury induced by SEV. Nerve injury was induced in rats by 3% SEV, and H19-7 was used to establish a pathological model, and sh-Trim47 was transfected into H19-7 to study the function of Trim47. The effects of SEV on the expression of Trim47 in the hippocampus and cognitive function of rats were studied by neurological function score and Moris water maze (MWM). The mRNA and protein expression of TNF-α, IL-1β and IL-6 in the cells, along with the neuronal apoptosis in the hippocampus of rats in each group were studied by TUNEL or WB. Flow cytometry was used to study the effect of knockdown of Trim47 on cell apoptosis. CCK-8 was used to detect cell viability of H19-7 cells. Finally, the potential signaling pathway affected by knockdown of Trim47 after abrogation of SEV induction was investigated by WB. The results showed that, knockdown of Trim47 ameliorated SEV-induced neurological damage and cognitive deficits, inflammation and neuronal cell apoptosis in rats, and promoted hippocampal neuronal activity. Knockdown of Trim47 can inhibit the NF-κB signaling pathway and improve neuronal cell damage and cognitive impairment induced by SEV in neonatal rats by regulating NF-κB signaling pathway, alleviating inflammatory response, and inhibiting neuronal apoptosis.

The expression of TRIM47, a member of the TRIM protein and E3 ubiquitin ligase families, is elevated in various cancers, such as non-small cell lung cancer and colorectal cancer, and is linked to poor prognosis. This study aimed to investigate the role of TRIM47 in gastric cancer development. Using The Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) dataset and analysis of 20 patient samples from our center, TRIM47 was found to be significantly up-regulated in gastric cancer tissues and associated with advanced N-stage and poor prognosis. We constructed stable TRIM47 knockdown and overexpressing gastric cancer cell lines. CCK8, EDU, colony formation, wound healing, and Transwell tests were used to evaluate the effects on cell proliferation, invasion, and migration. The results showed that TRIM47 knockdown inhibited the proliferation, migration and invasion of gastric cancer cells, while TRIM47 overexpression promoted these behaviors. These results were further confirmed in vivo. In the mechanism part, we found that TRIM47 interacts with CYLD protein. Moreover, TRIM47 promotes K48-linked ubiquitination, leading to the degradation of CYLD by the proteasome, thereby activating the NF-κB pathway and regulating the biological behavior of gastric cancer cells. Taken together, our study demonstrated that TRIM47 is involved in the proliferation and metastasis of gastric cancer through the CYLD/NF-κB pathway.

Background Renal cell carcinoma (RCC) is one of the most common malignant tumors originating from the renal parenchymal urinary epithelial system. Tripartite motif 47 (TRIM47) is a member of the TRIM family proteins, which has E3 ligase activity and has been demonstrated to be involved in the occurrence and prognosis of many tumors. The main purpose of this study is to explore the role and potential mechanism of TRIM47 in promoting malignant biological behavior of RCC. Materials and methods TRIM47 mRNA and protein levels in human renal cancer and paired normal adjacent tissues were detected by qRT-PCR and Western blot. The effects of TRIM47 knockdown and overexpression in renal cell carcinoma cells on cell proliferation, invasion and xenograft tumor growth in nude mice were analyzed. The molecular mechanism was explored by mass spectrometric exploration,Western blot and immunoprecipitation assays. Results TRIM47 promoted RCC cell proliferation in vitro and in vivo as an oncogene. Mechanistically, TRIM47 exerted an E3 ligase activity by interacting with P53 protein to increase its ubiquitination and degradation, which further promoted the malignant biological behavior of RCC. Conclusions Our study demonstrated that the TRIM47-P53 axis played a functional role in RCC progression and suggested a potential therapeutic target for RCC.

Background: The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma (HCC) remains unclear. This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis, immune response, and drug sensitivity. Methods: Data were obtained from The Cancer Genome Atlas (TCGA)-Hepatocellular Carcinoma (LIHC) and Gene Expression Omnibus (GEO, GSE14520 datasets). 47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. After classifying HCC samples using the Non-negative Matrix Factorization (NMF) clustering method, differentially expressed genes were screened. Then, 8 risk genes were obtained by univariate analysis, survival random forest reduction and lasso analysis. The expression of 8 risk genes was verified in vitro. Results: 8 risk genes were used to construct the Sphingolipid score model. High-Sphingolipid score predicted poor prognosis of HCC patients. Sphingolipid score was associated with immune checkpoints (IL-1B, TLR4, TGFB1, and IL-10), immune cells (Th2, Treg, MDSC, Neutrophil, Fibroblasts and macrophage), and MAPK Cascade. In the High-Sphingolipid score group, a significantly higher proportion of patients with TP53 (p53) mutations was significantly higher (56%). Furthermore, patients with a high-Sphingolipid score were predicted to have a higher sensitivity to chemotherapy drugs. In vitro validation showed that compared with normal liver cells LX-2, TRIM47, and S100A9 significantly increased in liver cancer cells Hep G2, MHCC-97H, and Hep3B2.1-7, while SLC1A7, LPCAT1, and CFHR4 significantly decreased. Silencing TRIM47 reduced the proliferation and promoted apoptosis. The levels of ceramide synthesis-related indexes (CERS1, CERS6, CERS5, and SPTLC2) increased, and the ACER3 related to catalytic hydrolysis decreased. Conclusion: We constructed a sphingolipid metabolism-related prognostic signature (Sphingolipid score) based on 8 risk genes. TRIM47 may affect the development of liver cancer by regulating the relevant indicators of ceramide synthesis and catalytic hydrolysis.

The Ubiquitin Proteasome System (UPS) has been shown to regulate neuronal development and synapse formation. Activity-dependent regulation of E3 ligase, a component of the UPS that targets specific proteins for proteasome-mediated degradation, is emerging as a pivotal player for the establishment of functional synapses. Here, we identified TRIM47 as a developmentally regulated E3 ligase that is expressed in rat hippocampus during the temporal window of synapse formation. We have demonstrated that the expression of TRIM47 is regulated by the glutamate-induced synaptic activity of hippocampal neurons in culture. In addition, the activity-dependent enhancement of TRIM47 expression is recapitulated following the object location test, a hippocampus-dependent spatial memory paradigm. We observed that this enhancement of TRIM47 expression requires NMDA receptor activation. The knockdown of TRIM47 leads to an enhancement of spine density without affecting dendritic complexity. Furthermore, we observed an increase in excitatory synapse development upon loss of TRIM47 function. Comprehensively, our study identified an activity-regulated E3 ligase that drives excitatory synapse formation in hippocampal neurons.

Increasing attention has been paid to the biological roles of tripartite motif-containing (TRIM) family proteins, which typically function as E3 ubiquitin ligases. Estrogen-responsive finger protein (Efp), a member of the TRIM family proteins, also known as TRIM25, was originally identified as a protein induced by estrogen and plays critical roles in promoting endocrine-related cancers, including breast cancer, endometrial cancer, and prostate cancer. The pathophysiological importance of Efp made us interested in the roles of other TRIM family proteins that share a similar structure with Efp. Based on a phylogenetic analysis of the C-terminal region of TRIM family proteins, we focused on TRIM47 as a protein belonging to the same branch as Efp. TRIM47 is a poor prognostic factor in both breast cancer and prostate cancer. Atypical lysine-27-like poly-ubiquitination was involved in the underlying mechanism causing endocrine resistance in breast cancer. We also discuss the functions of Efp and TRIM47 in other types of cancers and innate immunity by introducing substrates the are modified by poly-ubiquitination.