Tripartite Motif-containing 44 Research Articles

TRIM44 Promotes Endometrial Carcinoma Progression by Activating the FRS2 Signalling Pathway.

The Tripartite Motif Containing 44 (TRIM44) is highly expressed in a variety of tumours. However, the TRIM44's role in endometrial carcinoma (EC) progression remains unknown. To investigate the TRIM44's role in the development and metastasis of EC, we detected TRIM44 expression in EC cell lines and surgical specimens from patients with EC using immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and western blotting analysis. The biological functions of TRIM44 by loss-of-function analysis in RL95-2 and Ishikawa cells were studied. The effect of TRIM44 on the progression of EC in terms of cell proliferation, apoptosis, and invasion was examined and revealed its underlying mechanism in vitro using EC cell lines and in vivo using mouse xenograft models. The TRIM44's expression was positively correlated with EC progression and poor prognosis. The TRIM44 knockdown reduced the EC cell proliferation and invasion while promoting cell apoptosis. Mechanism experiments showed that the TRIM44 interacts with Fibroblast Growth Factor Receptor Substrate 2 (FRS2) and negatively regulates the expression of Bone Morphogenetic Protein 4(BMP4), β-catenin, and Transforming Growth Factor Beta Receptor 1(TGF-βR1). Moreover, the effect of TRIM44 overexpression on EC cell proliferation, invasion, and apoptosis is reversed by the FRS2 knockdown. Our study may provide a new perspective on targeting the TRIM44/FRS2 signaling pathway in treating EC, which deserves further investigation.

Silencing of TRIM44 Inhibits Inflammation and Alleviates Traumatic Brain Injury in Rats by Downregulating TLR4-NF-κB Signaling

Background: Neuroinflammation subsequent to traumatic brain injury (TBI) is important for the recovery of patients and is associated with neurodegenerative changes post-TBI. The tripartite motif containing 44 (TRIM44) protein is an E3 ligase involved in the regulation of immune function with no previously known link to TBI. This study explores the connection between TRIM44 and TBI. Methods: After induction of TBI in rats by control cortex injury, TRIM44 expressions were determined with quantitative real-time reverse transcription polymerase chain reaction and Western blot, and Toll-like receptor 4 (TLR4)-NF-κB signaling was examined by the expression of TLR4, p65 phosphorylation, and the specific NF-κB transcription activity. The effects of TRIM44 knockdown on inflammation, neurological function, and TLR4-NF-κB signaling in TBI rats were revealed by the detection of proinflammatory cytokines and TLR4-NF-κB signaling molecules, modified neurological severity score, brain water content, and Evans blue permeability. Results: We found that TRIM44 expression was significantly increased following TBI induction along with TLR4-NF-κB activation. Silencing of TRIM44 suppressed proinflammatory cytokine production, improved neurological outcomes, alleviated brain edema, and inhibited TLR4-NF-κB signaling in TBI rats. Conclusion: Our findings suggest that suppressing TRIM44 or modulation of relevant pathways may be a therapeutic strategy for TBI.

Clinical Significance of TRIM44 Expression in Patients with Gastric Cancer.

Background:Despite the tremendous efforts in finding a valuable markers for risk stratifying gastric cancer (GC) patients; still, management of this cancer faces multiple obstacles. Given this, we designed a study to explore the possible relationship between the tripartite motif-containing 44 (TRIM44) gene expression, and the outcome of the GC patients. Methods:The real-time quantitative PCR method was used to evaluate the mRNA expression level of TRIM44, and β-catenin in fresh primary tumor and adjacent normal tissues collected from 40 GC patients. The Pearson’s correlation test, Kaplan–Meier method, and Cox proportional-hazards regression were performed to examine the association of TRIM44 expression with some clinicopathological data and the patients’ overall survival (OS). Results:The expression level of both TRIM44 and β-catenin was remarkably higher in GC tissues than in normal tissues (Fold change=1.71, p=0.004). In subgroup analysis based on the TRIM44 expression, pateints with high TRIM44 expression level exhibited poorer overall survival (HR = 1.46, 95% CI: 1.07-1.98, p=0.016). More strikingly, a positive correlation was also found between the expression of TRIM44 and β-catenin in GC, indicating that TRIM44 might exert its oncogenic activities probably through the β-catenin axis. Conclusion:This study highlighted the potent value of TRIM44 as an independent prognostic factor in gastric cancer and shed light on the probable interplay between this tripartite motif-containing protein and β-catenin. However, further investigations, especially with a larger sample size, are required to study the effect of TRIM44 in GC more precisely.

CircFBXW8 Acts an Oncogenic Role in the Malignant Progression of Non-small Cell Lung Carcinoma by miR-370-3p-Dependent Regulation of TRIM44.

Non-small cell lung carcinoma (NSCLC) is an aggressive malignant tumor. Growing evidences have revealed that circular RNA (circRNA) is involved in NSCLC progression. This study aims to investigate the role of circular RNA F-box and WD repeat domain containing 8 (circFBXW8) in NSCLC progression and the underlying mechanism. The expression of circFBXW8, microRNA-370-3p (miR-370-3p) and tripartite motif containing 44 (TRIM44) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was detected by western blot analysis or immunohistochemistry assay. Additionally, cell viability, colony-forming ability, proliferation and apoptosis were investigated by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide, cell colony formation, 5-Ethynyl-29-deoxyuridine and flow cytometry analysis assays, respectively. Cell migratory and invasive abilities were examined by wound-healing and transwell assays. The regulatory relationship between miR-370-3p and circFBXW8 or TRIM44 was identified by dual-luciferase reporter and RNA pull-down assays. Furthermore, xenograft experiment was employed to explain the effect of circFBXW8 silencing on tumor formation. CircFBXW8 and TRIM44 expression were upregulated, while miR-370-3p was downregulated in NSCLC tissues, cells and the exosomes from NSCLC cells compared with respective controls. CircFBXW8 depletion repressed NSCLC cell proliferation, migration and invasion, but promoted cell apoptosis. CircFBXW8 acted as a sponge of miR-370-3p and regulated NSCLC cell malignancy by binding to miR-370-3p. Additionally, miR-370-3p repressed NSCLC cell processes by regulating TRIM44. CircFBXW8 knockdown inhibited tumor formation in vivo. Further, circFBXW8 secretion was mediated by exosomes. CircFBXW8 modulated NSCLC progression by increasing TRIM44 expression through sponging miR-370-3p, which provided a new direction for studying the therapy of NSCLC.

TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA.

Tripartite motif-containing 44 (TRIM44) has recently been implicated in various pathological processes in numerous cancers, including lung adenocarcinoma (LUAD); however, its functional roles in chemoresistance are poorly understood. Herein, TRIM44 knockdown sensitized LUAD cells to cisplatin and enhanced cisplatin-induced apoptosis. Microarray analysis indicated that the “Role of BRCA1 in DNA damage” and the BRCA1 gene expression were positively regulated by TRIM44, which was further verified by immunofluorescence, qRT-PCR, and Western blotting. BRCA1 depletion effectively abolished TRIM44-modulated cisplatin resistance and regulation of homologous recombination (HR) repair. Interestingly, TRIM44 interacted with FLNA, an upstream regulator of BRCA1 as specified by STRING V 11.5, and facilitated its stability and deubiquitination. FLNA was also found to be required for the functions of TRIM44 in drug resistance. Using animal models, overexpression of TRIM44 was shown to confer resistance to cisplatin in a BRCA1- and FLNA-dependent manner. TRIM44 expression levels in tissues from cisplatin-resistant LUAD patients were significantly higher than those in tissues from cisplatin-sensitive LUAD patients. Collectively, our study results demonstrate that the TRIM44/FLNA/BRCA1 axis is involved in cisplatin chemoresistance, providing potential therapeutic targets for LUAD patients with cisplatin resistance.

Sesamin exerts anti‐tumor activity in esophageal squamous cell carcinoma via inhibition of TRIM44 and NF‐κB signaling

Tripartite motif-containing 44 (TRIM44) is known to play an oncogenic role in multiple human cancers, including esophageal cancer. Sesamin possesses potent anti-inflammatory and anti-cancer properties for various cancers. This study is designed to unravel the biological functions of sesamin and TRIM44 in esophageal cancer. TRIM44 expression in esophageal squamous cell cancer (ESCC) cell lines and tissues was determined by RT-qPCR assay and Western blot. The effects of sesamin and TRIM44 on ESCC cell growth in vivo and in vitro were assessed by the mouse model and CCK-8 assay, respectively. We found that TRIM44 was significantly upregulated in ESCC cell lines and tissues when compared to their counterparts. Sesamin treatment or depletion of TRIM44 markedly reduced ESCC cell proliferation. The nuclear factor kappa B (NF-κB) and toll-like receptor 4 (TLR4) signaling pathway may be involved in sesamin-mediated TRIM44 suppression. Finally, we showed that oral administration of sesamin dramatically inhibited tumor growth or ESCC in nude mice. Our results suggest that sesamin exerts anti-tumor activity in ESCC via inhibition of NF-κB signaling pathway, demonstrating its potential for the treatment of esophageal cancer.

TRIM44 links the UPS to SQSTM1/p62-dependent aggrephagy and removing misfolded proteins

ABSTRACT Until recently, the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy were considered to be two independent systems that target proteins for degradation by proteasomes or via lysosomes, respectively. Here, we report that TRIM44 (tripartite motif containing 44) is a novel link that connects the UPS system with the autophagy degradation pathway. Suppressing the UPS degradation pathway leads to TRIM44 upregulation, which further promotes aggregated protein clearance through the binding of K48 ubiquitin chains on proteins. TRIM44 expression activates autophagy via promoting SQSTM1/p62 oligomerization, which rapidly increases the rate of aggregate protein removal. Overall, our data reveal that TRIM44 is a newly identified link between the UPS system and the autophagy pathway. Delineating the cross-talk between these two degradation pathways may reveal new mechanisms of targeting aggregate-prone diseases, such as cancer and neurodegenerative disease. Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; ATG5: autophagy related 5; BB: B-box domain; BECN1: beclin1; BM: bone marrow; CC: coiled-coil domain; CFTR: cystic fibrosis transmembrane conductance regulator; CON: control; CQ: chloroquine; DOX: doxycycline; DSP: dithiobis(succinimidly propionate); ER: endoplasmic reticulum; FI: fluorescence intensity; FL: full length; HIF1A/HIF-1#x3B1;: hypoxia inducible factor 1 subunit alpha; HSC: hematopoietic stem cells; HTT: huntingtin; KD: knockdown; KD-CON: knockdown construct control; MM: multiple myeloma; MTOR: mechanistic target of rapamycin kinase; NP-40: nonidet P-40; NFE2L2/NRF2: nuclear factor, erythroid 2 like 2; OE: overexpression; OE-CON: overexpression construct control; PARP: poly (ADP-ribose) polymerase; SDS: sodium dodecyl sulfate; SQSTM1/p62: sequestosome 1; Tet-on: tetracycline; TRIM44: tripartite motif containing 44; UPS: ubiquitin-proteasome system; ZF: zinc-finger

TRIM44 mediated p62 deubiquitination enhances DNA damage repair by increasing nuclear FLNA and 53BP1 expression.

Cancer cells show increases in protein degradation pathways, including autophagy, during progression to meet the increased protein degradation demand and support cell survival. On the other hand, reduced autophagy activity during aging is associated with a reduced DNA damage response and increased genomic instability. Therefore, it is a puzzling how DNA repair can be increased in cancer cells that are resistant to chemotherapies or during progression when autophagy activity is intact or increased. We discovered that tripartite motif containing 44 (TRIM44) is a pivotal element regulating the DNA damage response in cancer cells with intact autophagy. TRIM44 deubiquitinates p62, an autophagy substrate, which leads to its oligomerization. This prevents p62 localization to the nucleus upon irradiation. Increased cytoplasmic retention of p62 by TRIM44 prevents the degradation of FLNA and 53BP1, which increases DNA damage repair. Together, our data support TRIM44 a potential therapeutic target for therapy-resistant tumor cells with intact autophagy.

Circ_0030018 promotes glioma proliferation and metastasis.

BackgroundCircular RNA (circRNA) plays an essential role in tumor progression, including glioma. circ_0030018 is a newly discovered circRNA that is highly expressed in glioma. However, its role and mechanism in glioma need to be further elucidated.MethodsThe expression of circ_0030018, microRNA (miR)-194-5p, and tripartite motif containing 44 (TRIM44) was examined using quantitative real-time PCR. Cell proliferation, migration, invasion, and apoptosis were determined using MTT assay, colony formation assay, transwell assay, and flow cytometry. Moreover, dual-luciferase reporter assay and RNA pull-down assay were used to verify the interactions among circ_0030018, miR-194-5p, and TRIM44. The protein expression of TRIM44 was assessed by western blot analysis. Animal experiments were conducted to explore the role of circ_0030018 in glioma tumor growth in vivo.Resultscirc_0030018 was overexpressed in glioma tissues and cells, and its silencing could inhibit glioma cell proliferation, migration, invasion, and accelerate apoptosis. miR-194-5p could be sponged by circ_0030018, and its overexpression could hinder the progression of glioma cells. Further experiments revealed that miR-194-5p inhibitor reversed the negative regulation of circ_0030018 knockdown on glioma cell progression. In addition, TRIM44 was a target of miR-194-5p, and its downregulation could repress glioma cell progression. Overexpressed TRIM44 reversed the inhibition effect of miR-194-5p on glioma cell progression. Animal experiments suggested that circ_0030018 knockdown could reduce glioma tumor growth through regulating miR-194-5p and TRIM44.ConclusionOur 8data showed that circ_0030018 enhanced glioma progression by sponging miR-194-5p to regulate TRIM44, indicating that circ_0030018 might be a potential treatment target for glioma.

Circular RNA circWDR27 Promotes Papillary Thyroid Cancer Progression by Regulating miR-215-5p/TRIM44 Axis.

PurposeThis study was to explore the biological roles and underlying mechanism of circRNA WD repeat domain 27 (circWDR27).MethodsThe expression of circWDR27, microRNA-215-5p (miR-215-5p) and tripartite motif containing 44 (TRIM44) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays were employed to detect cell proliferation. Flow cytometry was used to determine cell apoptosis and cell cycle distribution. Cell migration and invasion abilities were examined by wound healing and transwell assays. The protein levels of matrix metalloproteinase 2 (MMP2), MMP9 and TRIM44 were analyzed by Western blot assay. The relationship between miR-215-5p and circWDR27 or TRIM44 was predicted by bioinformatics tools and confirmed using dual-luciferase reporter assay. Mouse xenograft model was established to examine the role of circWDR27 in vivo.ResultsCircWDR27 and TRIM44 were highly expressed while miR-215-5p was lowly expressed in PTC tissues and cells. Knockdown of circWDR27 suppressed cell proliferation and metastasis and induced cell cycle arrest and apoptosis in PTC cells. Moreover, miR-215-5p was a direct target of circWDR27, and its inhibition reversed the suppressive effect of circWDR27 knockdown on PTC cell progression. In addition, miR-215-5p directly targeted TRIM44, and miR-215-5p exerted its anti-cancer role in PTC cells by targeting TRIM44. Furthermore, circWDR27 positively regulated TRIM44 expression by sponging miR-215-5p. Importantly, knockdown of circWDR27 suppressed tumor growth in vivo by upregulating miR-215-5p and downregulating TRIM44.ConclusionCircWDR27 accelerates PTC progression via regulating miR-215-5p/TRIM44 axis, providing a potential therapeutic target for PTC.

Circ_0056285 Regulates Proliferation, Apoptosis and Glycolysis of Osteosarcoma Cells via miR-1244/TRIM44 Axis.

BackgroundOsteosarcoma (OS) is a common malignant bone cancer that occurs in adolescents and children. Circular RNAs (circRNAs) are important regulators of tumorigenesis and development. This study aimed to explore the role and molecular basis of circ_0056285 in OS.MethodsThe levels of circ_0056285, miR-1244 and tripartite motif containing 44 (TRIM44) were determined by quantitative real-time polymerase chain reaction or Western blot assay. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell apoptosis was assessed by flow cytometry and caspase 3and caspase 9 activity assay kits. Glucose uptake, lactate product and ATP level were examined using commercial kits. Hexokinase II (HK2) and lactate dehydrogenase A (LDHA) levels were measured by Western blot assay. The interaction among circ_0056285, miR-1244 and TRIM44 was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation assay or RNA pull-down assay. Xenograft experiment was conducted to explore tumor growth in vivo. Exosomes were identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western blot. The diagnostic value of exosomal circ_0056285 was evaluated by receiver operating characteristic (ROC) curve.ResultsCirc_0056285 and TRIM44 were up-regulated, and miR-1244 was down-regulated in OS tissues and cells. Circ_0056285 silencing inhibited proliferation and glycolysis and promoted apoptosis in OS cells. Also, circ_0056285 knockdown hindered proliferation and accelerated apoptosis in OS cells by regulating miR-1244/TRIM44 axis. Circ_0056285 depletion impeded tumor growth in vivo. Furthermore, ROC curve showed that circ_0056285 might be a diagnostic biomarker in OS.ConclusionCirc_0056285 facilitated OS progression by sponging miR-1244 and increasing TRIM44 expression, providing a promising therapeutic target for OS.

Tripartite Motif-Containing 44 is Involved in the Tumorigenesis of Laryngeal Squamous Cell Carcinoma, and its Expression is Downregulated by Nuciferine.

Tripartite motif-containing 44 (TRIM44) was reported to be involved in the tumorigenesis of several tumors, but its function in laryngeal squamous cell carcinoma has not been investigated yet. In the present study, we aimed to elucidate the function of TRIM44 in laryngeal squamous cell carcinoma, and identify the compounds which could inhibit TRIM44 expression. Our results showed that TRIM44 was upregulated in tumor tissues and cell lines of laryngeal squamous cell carcinoma. Knockdown of TRIM44 significantly inhibited cell growth of laryngeal squamous cell carcinoma by suppressing TLR4, phosphorylated AKT and phosphorylated NF-κB p65 expression in vitro. Moreover, TRIM44 knockdown inhibited tumor growth in nude mice, which further suggested that TRIM44 exerted oncogenic activity in laryngeal squamous cell carcinoma. Interestingly, it was found that nuciferine significantly inhibited the mRNA levels of TRIM44 after screening a small natural compound library. Our further studies showed nuciferine markedly downregulated the protein levels of TRIM44 and its substrate TLR4 in a concentration-dependent manner in laryngeal squamous cell carcinoma cells. Moreover, the activation of downstream kinases of TLR4 such as AKT signaling pathway was also inhibited by nuciferine. Additionally, nuciferine markedly inhibited cell survival of laryngeal squamous cell carcinoma in a concentration-dependent manner. In contrast, TRIM44 overexpression significantly reduced the cytotoxicity of nuciferine in laryngeal squamous cell carcinoma cells. In conclusion, this study indicated that inhibiting TRIM44 would be a useful strategy for the treatment of laryngeal squamous cell carcinoma, and nuciferine could be a potential chemical applicated in the therapy of laryngeal squamous cell carcinoma.

Inhibition of SPATS2 Suppresses Proliferation and Invasion of Hepatocellular Carcinoma Cells through TRIM44-STAT3 Signaling Pathway.

Hepatocellular carcinoma (HCC) is a major global health burden and its treatment options are limited. Spermatogenesis associated serine rich 2(SPATS2), a recent defined oncogene, was found to be a prognostic biomarker in HCC. However, the explicit mechanism underlying SPATS2 was urged to be elucidated. In vitro, knockdown of SPATS2 hampered the proliferation, invasion and migration of HCC cells. Moreover, phosphorylation of signal transducer and activator of transcription 3 (STAT3) and its downstream oncogenes were dramatically suppressed by SPATS2 knockdown. In addition, tripartite motif containing 44 (TRIM44) was found to be positively associated with SPATS2 in TCGA and declined after SPATS2 knockdown in HCC cells. Overexpression of TRIM44 rescued the effect of SPATS2 silencing on p-STAT3 and its downstream oncogenes. In vivo, SPATS2 silencing was confirmed to impede HCC tumor development in nude mice. In our own cohort containing 112 HCC patients, high SPATS2 protein level is indicative of an unfavorable clinicopathological feature and poor prognosis and could serve as an independent risk factor. Collectively, the present study is the first to propose the mechanism of significance of SPATS2-TRIM44-p-STAT3 in HCC and provide a new theoretical basis for targeted therapy.

Combined A20 and tripartite motif-containing 44 as poor prognostic factors for breast cancer patients of the Japanese population.

We previously reported that a strong immunoreactivity of tripartite motif-containing 44 (TRIM44) predicts the poor prognosis of patients with invasive breast cancer, and proposed that TRIM44 activates nuclear factor-κB (NF-κB) signaling as a causative mechanism. In the present study, we examined the clinicopathological roles of A20, which is known to be an NF-κB responsive gene, with TRIM44, in an updated cohort. Tissue samples of invasive breast cancer were obtained from 140 Japanese female breast cancer patients who underwent surgical treatment. Immunoreactivities of A20 and TRIM44 were analyzed using specific antibodies for each protein. A positive A20 immunoreactivity was significantly associated with a shorter disease-free survival (P = 0.043) and was positively correlated with TRIM44 immunoreactivity (P = 0.039). Combined use of the immunoreactivities for two proteins revealed that double-positive status for both A20 and TRIM44 immunoreactivities was associated with a shorter disease-free survival (P = 0.012) and was an independent factor for poor prognosis. These results indicate that a combined A20 and TRIM44 immunoreactivity predicted the prognosis of patients with invasive breast cancer. Moreover, the positive correlation between A20 and TRIM44 immunoreactivities suggested that the activation of NF-κB signaling by TRIM44 could occur in clinical breast cancer tissues.

The Novel Target of Colorectal Carcinoma: TRIM44 Regulates Cell Migration and Invasion via Activation of CXCR4/NF-κB Signaling.

Tripartite motif containing 44 (TRIM44) has been reported to regulate various biological effects in malignant cancers and matrix Metalloproteinases has been demonstrated to be associated with cancer cell migration and invasion. Nonetheless, the expression and molecular mechanism of TRIM44 in colorectal cancer (CRC) remain rarely known. TRIM44 was overexpressed or knocked down in CRC cells. Subsequently, the effects of TRIM44 on cell migration and invasion as well as underlying molecular mechanisms were detected. Data showed that TRIM44 was highly expressed in CRC cell lines. Downregulation of TRIM44 inhibited the cell viability, migration, and invasion in SW-480 cells. In addition, overexpression of TRIM44 enhanced the expression of NF-κB and CXCR4, and enhanced the binding between NF-κB and CXCR4 promoter region. In summarize, TRIM44 may serve as a potential target for CRC diagnosis and progression.

Expression of tripartite motif-containing 44 and its prognostic and clinicopathological value in human malignancies:a meta-analysis

BackgroundPrevious researches have reported that tripartite motif-containing 44 (TRIM44) is related to the prognosis of multiple human tumors. This study was designed to systematically assess the prognostic value of TRIM44 in human malignancies and summarize its possible tumor-related mechanisms.MethodsThe available databases were searched for eligible studies that evaluated the clinicopathological and prognostic roles of TRIM44 in patients with malignancies. The hazard ratios (HR) and odds ratios (OR) were combined to assess the predictive role of TRIM44 using Stata/SE 14.1 software.ResultsA total of 1740 patients from thirteen original studies were finally included in this study. The results of the combined analysis showed that over-expression of TRIM44 protein was significantly correlated with shorter overall survival (OS) (HR = 1.94, 95% CI: 1.60–2.35) and worse disease-free survival (DFS) (HR = 2.13, 95% CI: 1.24–3.65) in cancer patients. Additionally, the combined ORs indicated that elevated expression level of TRIM44 protein was significantly associated with lymph node metastasis (OR = 2.69, 95% CI: 1.71–4.24), distant metastasis (OR = 10.35, 95% CI: 1.01–106.24), poor tumor differentiation (OR = 1.78, 95% CI: 1.03–3.09), increased depth of tumor invasion (OR = 2.72, 95% CI: 1.73–4.30), advanced clinical stage (OR = 2.75, 95% CI: 2.04–3.71), and recurrence (OR = 2.30, 95% CI: 1.34–3.95). Furthermore, analysis results using Gene Expression Profiling Interactive Analysis (GEPIA) showed that the expression level of TRIM44 mRNA was higher in most tumor tissues than in the corresponding normal tissues, and the relationship between TRIM44 mRNA level and prognosis in various malignant tumors also explored in GEPIA and OS analysis webservers.ConclusionsTRIM44 may serve as a valuable prognostic biomarker and a potential therapeutic target for patients with malignancies.

Knockdown of HIF1A-AS2 suppresses TRIM44 to protect cardiomyocytes against hypoxia-induced injury.

Myocardial infarction (MI) is a common cardiovascular disease characterized by an interruption of blood and oxygen supply to the heart, which results in gradual damage to the myocardial tissue and ultimately heart failure. The role of long non-coding RNAs in the pathology of MI remains in its infancy, but has been implicated in MI and other heart conditions. For example, the expression of a non-coding RNA hypoxia-inducible factor 1α (HIF1A)-antisense RNA 2 (HIF1A-AS2) has previously been linked to coronary heart disease, however, whether HIF1A-AS2 expression is also high in MI has not been addressed. Here, we report that HIF1A-AS2 is upregulated in hypoxia-treated human cardiomyocytes (HMCs) compared with normal cardiomyocytes, and that silenced HIF1A-AS2 inhibited apoptosis and facilitated viability, migration, and invasion of HMCs. Our data suggested that in MI, HIF1A-AS2 upregulation was associated with miR-623, which promoted expression of tripartite motif containing 44 (TRIM44). Moreover, by upregulating TRIM44 we were able to remedy the HIF1A-AS2 repression of apoptosis in HMCs. Thus, we conclude that cardiomyocytes can be protected against hypoxic-treated injury by knockdown of HIF1A-AS2, which suppresses TRIM44, and that HIF1A-AS2 overexpression is a prognostic indicator of MI.

High TRIM44 expression as a valuable biomarker for diagnosis and prognosis in cervical cancer.

Tripartite motif containing 44 (TRIM44) has been reported to be up-regulated in multiple aggressive malignant tumors. However, its expression status and clinical significance in cervical cancer remain unknown. The purpose of this study was to investigate the clinical significance of TRIM44 expression and the prognosis in patients with cervical cancer (CC). Fresh frozen tissues from 5 samples of CC and 4 normal cervical tissues were analyzed for TRIM44 expression using RT- PCR and Western blot analysis. 122 paraffin-embedded surgical specimens from patients with CC were collected for an immunohistochemistry. TRIM44 expression was found to be significantly up-regulated in cervical cancer specimens compared with adjacent normal tissues (P<0.001). Statistical analysis showed that TRIM44 expression was significantly correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and lymph node metastasis, but not with age, histological type, and tumor size. Kaplan–Meier survival analysis suggested that high TRIM44 expression was associated with poor prognosis. Patients highly expressing TRIM44 have significantly shorter overall survival (OS) (P=0.006) and disease-free survival (DFS) (P=0.002). Furthermore, multivariate Cox analysis showed TRIM44 was an independent risk factor for poor prognosis. Our study demonstrated that TRIM44 expression contributes to the progression of cervical cancer, and could be used as a marker of clinical diagnosis and prognosis of patients with cervical cancer.

TRIM44 promotes quiescent multiple myeloma cell occupancy and survival in the osteoblastic niche via HIF-1\u03b1 stabilization

Despite progress in the treatment of MM, including the use of high-dose chemotherapy and autologous stem cell transplantation, a considerable proportion of patients are refractory to all therapies. This resistance is related to the molecular genetic heterogeneity in MM cells as well as to the contributions from the BM, which is one of the key determinants of treatment outcome. Our previous studies using fluorescent tracers revealed that MM heterogeneity is correlated with the presence of quiescent stem-like cancer cells, which prefer to reside within the osteoblastic niche of the BM. In this report, we identified a novel protein, tripartite motif containing 44 (TRIM44), which is overexpressed in the osteoblastic niche of the BM, enabling MM cells to compete with HSCs for niche support. TRIM44 expression in MM cells promoted cell quiescence but increased bone destruction in xenograft mice, similar to what is observed in MM patients. TRIM44 functions as a deubiquitinase for hypoxia inducible factor-1α (HIF-1α), which stabilizes HIF-1α expression during hypoxia and normoxia. Stabilized HIF-1α stimulates MM cell growth and survival during hypoxia. Our work is the first report to reveal signaling in quiescent MM cells and the functions of TRIM44.

Overexpression of TRIM44 is an independent marker for predicting poor prognosis in epithelial ovarian cancer.

Tripartite motif-containing 44 (TRIM44) has been demonstrated to be important in tumor metastasis and progression. However, the expression pattern and prognostic value of the expression of TRIM44 in epithelial ovarian cancer (EOC) remain to be fully elucidated. In the present study, the aim was to investigate the expression and clinical role of TRIM44 in EOC. A total of 109 patients, who underwent primary surgery with the goal of maximal tumor resection followed by standard combination chemotherapy with carboplatin and paclitaxel, were analyzed in the present study. The expression level of TRIM44 was determined by western blot analysis and immunohistochemistry in 109 ECO tissues. It was found that the expression of TRIM44 was low in normal tissues and high in EOC tissues. Univariate survival analysis showed that the overexpression of TRIM44 was significantly associated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis (P<0.05). Kaplan-Meier analysis suggested that there was a significant difference in overall survival and disease-free survival rates between patients with a high expression of TRIM44 and patients with a low expression of TRIM44. Patients with a high expression level of TRIM44 exhibited poorer overall survival and disease-free survival rates, compared with patients expressing a low level of TRIM44 (P<0.001). In addition, the results of the multivariate analysis revealed that the predictive value of the expression of TRIM44 was independent of other clinicopathological factors for predicting prognosis. These findings demonstrated that a high expression of TRIM44 was associated with the progression and prognosis of EOC.