Impaired dNKAP function drives genome instability and tumorigenic growth in Drosophila epithelia.

Mutations or dysregulated expression of NF-kappaB activating protein (NKAP) family genes have been found in human cancers. How NKAP family gene mutations promote tumor initiation and progression remains to be determined. Here, we characterized dNKAP, the Drosophila homolog of NKAP, and showed that impaired dNKAP function causes genome instability and tumorigenic growth in a Drosophila epithelial tumor model. dNKAP-knockdown wing imaginal discs exhibit tumorigenic characteristics, including tissue overgrowth, cell invasive behavior, abnormal cell polarity, and cell adhesion defects. dNKAP knockdown causes both R-loop accumulation and DNA damage, indicating the disruption of genome integrity. Further analysis showed that dNKAP knockdown induces c-Jun N-terminal kinase (JNK)-dependent apoptosis and causes changes in cell proliferation in distinct cell populations. Activation of the Notch and JAK/STAT signaling pathways contributes to the tumorigenic growth of dNKAP-knockdown tissues. Furthermore, JNK signaling is essential for dNKAP depletion-mediated cell invasion. Transcriptome analysis of dNKAP-knockdown tissues confirmed the misregulation of signaling pathways involved in promoting tumorigenesis and revealed abnormal regulation of metabolic pathways. dNKAP knockdown and oncogenic Ras, Notch, or Yki mutations show synergies in driving tumorigenesis, further supporting the tumor-suppressive role of dNKAP. In summary, this study demonstrates that dNKAP plays a tumor-suppressive role by preventing genome instability in Drosophila epithelia and thus provides novel insights into the roles of human NKAP family genes in tumor initiation and progression.

Molecular Epidemiology of Carbapenem Resistant Klebsiella Pneumoniae in Northern China: Clinical Characteristics, Antimicrobial Resistance, Virulence and Geographic Distribution.

Purpose: In this article, we studied in detail 74 Carbapenem Resistant Klebsiella pneumoniae (CRKP) in Shanxi to provide essential insight into development of effective strategies for control of CRKP. Patients and Methods: From 2018 to 2021, we collected 74 clinical CRKP from 11 hospitals in Shanxi Province. Clinical data were obtained from medical records, and all isolates were subjected to antimicrobial susceptibility testing, multi locus sequence typing, capsular serotypes, resistant gene profiles and virulence gene profiles. The synergistic activity was performed by microdilution checkerboard method. Results: Our study found differences in the clinical characteristics of CRKP between regions in Shanxi. Sequence type (ST) 11 was the dominant ST in Shanxi; however, the ST types in Shanxi had become more diverse over time and the proportion of STs showed a more balanced distribution with a significant decrease in ST11. NDM was the most common carbapenemase in Shanxi. In addition, the STs, carbapenemases, serotypes and virulence gene distribution varied by region in Shanxi. Moreover, tigecycline in combination with carbapenems and aztreonam had an excellent synergistic effect on CRKP in vitro. Conclusion: The results of this study provide essential insight into development of effective strategies for control of CRKP in Shanxi.

Constructing asymmetric double-atomic sites for synergistic catalysis of electrochemical CO2 reduction.

Elucidating the synergistic catalytic mechanism between multiple active centers is of great significance for heterogeneous catalysis; however, finding the corresponding experimental evidence remains challenging owing to the complexity of catalyst structures and interface environment. Here we construct an asymmetric TeN2-CuN3 double-atomic site catalyst, which is analyzed via full-range synchrotron pair distribution function. In electrochemical CO2 reduction, the catalyst features a synergistic mechanism with the double-atomic site activating two key molecules: operando spectroscopy confirms that the Te center activates CO2, and the Cu center helps to dissociate H2O. The experimental and theoretical results reveal that the TeN2-CuN3 could cooperatively lower the energy barriers for the rate-determining step, promoting proton transfer kinetics. Therefore, the TeN2-CuN3 displays a broad potential range with high CO selectivity, improved kinetics and good stability. This work presents synthesis and characterization strategies for double-atomic site catalysts, and experimentally unveils the underpinning mechanism of synergistic catalysis.

[Translocation, Accumulation, and Comprehensive Risk Assessment of Heavy Metals in Soil-Crop Systems in an Old Industrial City, Shizuishan, Ningxia, Northwest China].

In order to explore the environmental geochemistry characteristics of heavy metals (HMs) in soil-crop systems in an old industrial city, the concentration and fraction of HMs in the paddy, wheat, and maize root soil and their seeds were detected and analyzed. Subsequently, statistical methods, risk assessment coding (RAC), the bio-enrichment coefficient factor (BCF), influence index of comprehensive quality (IICQ), and ArcGIS spatial interpolation were used to conduct the translocation, accumulation, and comprehensive risk assessment of HMs in soil-crop systems. The results showed that the average concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in root soil were ranked respectively as follows:12.56, 0.19, 63.48, 23.52, 0.038, 28.86, 21.68, and 69.47 mg·kg-1. HMs in root soil were accumulated to some extent in comparison with the soil background value in Ningxia, especially Cd and Hg, but did not exceed the soil environmental pollution screening value (GB 14618-2018). The average concentrations of the eight aforementioned elements in supporting crop seeds were 0.0149, 0.0112, 0.075, 6.7, 0.0015, 0.67, 0.0427, and 20.48 mg·kg-1 in turn. The over-limit ratio of As, Pb, and Cr in crop seeds was 4%, 3%, and 1%, respectively, relative to the national food safety standards (GB 2762-2017), whereas the other five elements were within the allowable range. In comparison to those in paddy and wheat, HMs hardly tended to translocate to maize seeds from root soil. According to the results of IICQ in soil-crop systems, the cultivated soil was in the state of slight sub-contamination regionally, and only 10% of sampling points showed slight (sub-)contamination-submoderate contamination, where we could replant maize to reduce HMs contamination risk.

Molecular Dynamic and Dissipative Particle Dynamic Simulation on the Miscibility of NR/CR Blends.

Natural rubber (NR) exhibits good elasticity, flexural resistance, wear resistance, and excellent mechanical properties, and it has been widely used in aerospace, transportation, medical, and health fields. For NR, however, the resistance to thermal-oxidation and ozone aging is fairly poor. Although aging properties of NR can be significantly improved with the incorporation of chloroprene rubber (CR) according to some references, the miscibility between NR and CR, the morphologies of the binary blends, and so on are revealed ambiguously. In this work, molecular dynamics simulation (MD) and dissipative particle dynamics (DPD) simulation were carried out to predict the compatibility between natural rubber and chloroprene rubber in view of Flory-Huggins parameters. The morphologies of the blends were obtained with the use of the DPD method. The simulation results were furtherly examined by means of Fourier transform infrared spectroscopy (FT-IR) and dynamic mechanical analysis (DMA). It was found that the miscibility between NR and CR is poor. Nevertheless, the miscibility could be improved when the content of CR is 50% or 90%. In addition, spinodal decomposition with a critical temperature of 390 K would take place according to the phase diagram. Microphase structure such as spherical, lamellar, and bicontinuous phases can be found with different contents of CR in the blends with the results of morphologies analysis.

[Threshold of Se-rich Soil Based on Available-Se and Influencing Factors of Available-Se].

Available selenium (Se) in soil was the predominant factor affecting the content of Se in crops. In order to reasonably delineate the Se-rich soil range and propose theoretical guidance for the cultivation of natural Se-rich crops in a region where the surface soils had a high level of available-Se and a low level of total-Se, 8814 samples in surface soil and 195 root-crop matching samples were collected in Shizuishan in northern Ningxia. On the basis of the main line of analysis of available-Se, the following research was conducted: by synthetically studying the total-Se and available-Se in surface soil and root soil, the morphology of Se in surface soil, as well as Se in crops, deep and coordinated analyses of content among total-Se, available-Se, and Se in root-crop matching samples were carried out, and the suitable threshold for Shizuishan was confirmed. A multiple regression model of available-Se was established to determine the main physical and chemical indexes affecting available-Se, which were expected to improve the Se enrichment rate of crops through the enhancement of available-Se. The results demonstrated that ω(Se) and ω(Seavailable)in the surface soil in Shizuishan were 0.26 mg·kg-1 and 12.85 µg·kg-1, respectively, and the characteristics of Se and available-Se in root-crop matching samples could represent those in surface soil. Thus, it was recommended to use 0.24 mg·kg-1 as the suitable threshold of Se-rich soil. The multiple regression model of available-Se showed that the increase in total-Se and soil elements affecting soil fertility could promote the enrichment of available-Se.

Microbial community analyses provide a differential diagnosis for the antemortem and postmortem injury of decayed cadaver: An animal model.

Differentiating antemortem injury from postmortem injury of decayed cadavers is one of the difficult issues in forensic science. Forensic pathologists identify antemortem injury according to the macroscopic and microscopic vital reactions taken place after being injured. However, the decomposition would render those vital reactions ineffective. Microbiomes have been widely used in forensic science due to their succession with time and sensitivity to vary of environment. In this study, microbiomes were introduced to determine whether the bacterial communities can be used to distinguish between the ante- and postmortem injuries through an animal experiment. Our findings showed that the differences of bacterial community were increasingly apparent from the 6th to 9th day after the wound created when the types of wounds were unidentified by morphological examination due to decomposition. The biomarkers at the genus level could effectively distinguish between injury types, Among them, Enterococcus and Enterobacter were only observed in the antemortem injured group, while Staphylococcus and Acinetobacter were only in the postmortem injured group. It is possible to tell whether cadaveric injuries developed before or after death by detecting differences in the bacterial communities of putrefying wounds. This study provides a new perspective for the differences between ante- and postmortem injuries and provides a promising method for us to identify the ante- and postmortem wounds, especially in decomposed cadavers.

Initial CT-based radiomics nomogram for predicting in-hospital mortality in patients with traumatic brain injury: a multicenter development and validation study.

OBJECTIVE: To develop and validate a radiomic prediction model using initial noncontrast computed tomography (CT) at admission to predict in-hospital mortality in patients with traumatic brain injury (TBI). METHODS: A total of 379 TBI patients from three cohorts were categorized into training, internal validation, and external validation sets. After filtering the unstable features with the minimum redundancy maximum relevance approach, the CT-based radiomics signature was selected by using the least absolute shrinkage and selection operator (LASSO) approach. A personalized predictive nomogram incorporating the radiomic signature and clinical features was developed using a multivariate logistic model to predict in-hospital mortality in patients with TBI. The calibration, discrimination, and clinical usefulness of the radiomics signature and nomogram were evaluated. RESULTS: The radiomic signature consisting of 12 features had areas under the curve (AUCs) of 0.734, 0.716, and 0.706 in the prediction of in-hospital mortality in the internal and two external validation cohorts. The personalized predictive nomogram integrating the radiomic and clinical features demonstrated significant calibration and discrimination with AUCs of 0.843, 0.811, and 0.834 in the internal and two external validation cohorts. Based on decision curve analysis (DCA), both the radiomic features and nomogram were found to be clinically significant and useful. CONCLUSION: This predictive nomogram incorporating the CT-based radiomic signature and clinical features had maximum accuracy and played an optimized role in the early prediction of in-hospital mortality. The results of this study provide vital insights for the early warning of death in TBI patients.

Chinese Admission Warning Strategy for Predicting the Hospital Discharge Outcome in Patients with Traumatic Brain Injury.

OBJECTIVE: To develop and validate an admission warning strategy that incorporates the general emergency department indicators for predicting the hospital discharge outcome of patients with traumatic brain injury (TBI) in China. METHODS: This admission warning strategy was developed in a primary cohort that consisted of 605 patients with TBI who were admitted within 6 h of injury. The least absolute shrinkage and selection operator and multivariable logistic regression analysis were used to develop the early warning strategy of selected indicators. Two sub-cohorts consisting of 180 and 107 patients with TBI were used for the external validation. RESULTS: Indicators of the strategy included three categories: baseline characteristics, imaging and laboratory indicators. This strategy displayed good calibration and good discrimination. A high C-index was reached in the internal validation. The multicenter external validation cohort still showed good discrimination C-indices. Decision curve analysis (DCA) showed the actual needs of this strategy when the possibility threshold was 0.01 for the primary cohort, and at thresholds of 0.02-0.83 and 0.01-0.88 for the two sub-cohorts, respectively. In addition, this strategy exhibited a significant prognostic capacity compared to the traditional single predictors, and this optimization was also observed in two external validation cohorts. CONCLUSIONS: We developed and validated an admission warning strategy that can be quickly deployed in the emergency department. This strategy can be used as an ideal tool for predicting hospital discharge outcomes and providing objective evidence for early informed consent of the hospital discharge outcome to the family members of TBI patients.

Molecular mechanism of agonism and inverse agonism in ghrelin receptor.

Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are considered useful therapeutic agents, but the molecular mechanism of such ligands remains insufficiently understood. Here, we report a crystal structure of the ghrelin receptor bound to the inverse agonist PF-05190457 and a cryo-electron microscopy structure of the active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin. Our structures reveal a distinct binding mode of the inverse agonist PF-05190457 in the ghrelin receptor, different from the binding mode of agonists and neutral antagonists. Combining the structural comparisons and cellular function assays, we find that a polar network and a notable hydrophobic cluster are required for receptor activation and constitutive activity. Together, our study provides insights into the detailed mechanism of ghrelin receptor binding to agonists and inverse agonists, and paves the way to design specific ligands targeting ghrelin receptors.

CD146 bound to LCK promotes T cell receptor signaling and antitumor immune responses in mice.

Initiation of T cell receptor (TCR) signaling involves the activation of the tyrosine kinase LCK; however, it is currently unclear how LCK is recruited and activated. Here, we have identified the membrane protein CD146 as an essential member of the TCR network for LCK activation. CD146 deficiency in T cells substantially impaired thymocyte development and peripheral activation, both of which depend on TCR signaling. CD146 was found to directly interact with the SH3 domain of coreceptor-free LCK via its cytoplasmic domain. Interestingly, we found CD146 to be present in both monomeric and dimeric forms in T cells, with the dimerized form increasing after TCR ligation. Increased dimerized CD146 recruited LCK and promoted LCK autophosphorylation. In tumor models, CD146 deficiency dramatically impaired the antitumor response of T cells. Together, our data reveal an LCK activation mechanism for TCR initiation. We also underscore a rational intervention based on CD146 for tumor immunotherapy.

GNG5 is an unfavourable independent prognostic indicator of gliomas.

Gliomas are the most common primary brain tumours, and glioblastomas (GBMs) are subgrouped into four distinct molecular subtypes. This study aimed to identify the potential gene related to glioma progression. Weighted gene co-expression network analysis (WGCNA) was used to explore the related gene. Correlation, ROC, survival and Cox regression analyses were performed. Blue module was strongly associated with WHO grade (r = .65, P = 1e-19). GNG5 in gliomas was overexpressed compared with normal samples and associated with clinicopathologic characteristics. GNG5 was frequent in Mesenchymal subtype and lowly expressed in Proneural subtype of GBMs. Survival and Cox regression analyses showed that glioma patients with GNG5 overexpression had shorter survival time, and GNG5 was an independent prognostic indicator of overall survival. Overall, GNG5 expression is closely associated with clinicopathologic characteristics and is an independent prognostic indicator for glioma patients, as well as a promising subtype-associated biomarker in molecular classification of gliomas.

Integrated Transcriptomic Analysis Reveals the Molecular Mechanism of Meningiomas by Weighted Gene Coexpression Network Analysis.

Meningiomas are the most common primary intracranial tumor in adults. However, to date, systemic coexpression analyses for meningiomas fail to explain its pathogenesis. The aim of the present study was to construct coexpression modules and identify potential biomarkers associated with meningioma progression. Weighted gene coexpression network analysis (WGCNA) was performed based on GSE43290, and module preservation was tested by GSE74385. Functional annotations were performed to analyze biological significance. Hub genes were selected for efficacy evaluations and correlation analyses using two independent cohorts. A total of 14 coexpression modules were identified, and module lightcyan was significantly associated with WHO grades. Functional enrichment analyses of module lightcyan were associated with tumor pathogenesis. The top 10 hub genes were extracted. Ten biomarkers, particularly AHCYL2, FGL2, and KCNMA1, were significantly related to grades and prognosis of meningioma. These findings not only construct coexpression modules leading to the better understanding of its pathogenesis but also provide potential biomarkers that represent specific on tumor grades and identify recurrence, predicting prognosis and progression of meningiomas.

Integrated Transcriptome Analyses and Experimental Verifications of Mesenchymal-Associated TNFRSF1A as a Diagnostic and Prognostic Biomarker in Gliomas.

Gliomas are the most prevalent malignant primary brain tumors with poor outcome, and four different molecular subtypes (Mesenchymal, Proneural, Neural, and Classical) are popularly applied in scientific researches and clinics of gliomas. Public databases contain an abundant genome-wide resource to explore the potential biomarker and molecular mechanisms using the informatics analysis. The aim of this study was to discover the potential biomarker and investigate its effect in gliomas. Weighted gene co-expression network analysis (WGCNA) was used to construct the co-expression modules and explore the biomarker among the dataset CGGA mRNAseq_693 carrying 693 glioma samples. Functional annotations, ROC, correlation, survival, univariate, and multivariate Cox regression analyses were implemented to investigate the functional effect in gliomas, and molecular experiments in vitro were performed to study the biological effect on glioma pathogenesis. The brown module was found to be strongly related to WHO grade of gliomas, and KEGG pathway analysis demonstrated that TNFRSF1A was enriched in MAPK signaling pathway and TNF signaling pathway. Overexpressed TNFRSF1A was strongly related to clinical features such as WHO grade, and functioned as an independent poor prognostic predictor of glioma patients. Notably, TNFRSF1A was preferentially upregulated in the Mesenchymal subtype gliomas (Mesenchymal-associated). Knockdown of TNFRSF1A inhibited proliferation and migration of glioma cell lines in vitro. Our findings provide a further understanding of the progression of gliomas, and Mesenchymal-associated TNFRSF1A might be a promising target of diagnosis, therapy, and prognosis of gliomas.

Structure-guided discovery of a single-domain antibody agonist against human apelin receptor.

Developing antibody agonists targeting the human apelin receptor (APJ) is a promising therapeutic approach for the treatment of chronic heart failure. Here, we report the structure-guided discovery of a single-domain antibody (sdAb) agonist JN241-9, based on the cocrystal structure of APJ with an sdAb antagonist JN241, the first cocrystal structure of a class A G protein-coupled receptor (GPCR) with a functional antibody. As revealed by the structure, JN241 binds to the extracellular side of APJ, makes critical contacts with the second extracellular loop, and inserts the CDR3 into the ligand-binding pocket. We converted JN241 into a full agonist JN241-9 by inserting a tyrosine into the CDR3. Modeling and molecular dynamics simulation shed light on JN241-9-stimulated receptor activation, providing structural insights for finding agonistic antibodies against class A GPCRs.

The length and width of diatoms in drowning cases as the evidence of diatoms penetrating the alveoli-capillary barrier.

Forensic diatom test has been considered as a significant tool for diagnosis of drowning. Most of the studies in this field discussed the methodology of extracting, enriching and detecting diatoms from different tissues and drowning media. There are few studies on the basic principle of diatom test which was based on the theory developed by forensic scientists many years ago. This study was designed to analyze the length and width of diatoms in different organs and drowning medium samples of drowning cases. This study is designed to find evidence of diatoms penetrating the alveoli-capillary barrier. Samples from 100 drowning cases were analyzed using the methodology we developed: the Microwave Digestion-Vacuum Filtration-Automated Scanning Electron Microscopy method (MD-VF-Auto SEM method). The results showed that the length and width of diatoms in the liver and kidney tissues are smaller than that of the lung tissues and water samples. Our studies also found that the pennate diatoms are easier to penetrate through the alveoli-capillary barrier, travel in the blood stream and finally deposit in the distant tissues including liver and kidney. These findings provided evidences to support the process of diatoms penetrating the alveoli-capillary barrier.

BMX activates Wnt/ß-catenin signaling pathway to promote cell proliferation and migration in breast cancer.

BACKGROUND: Breast cancer has become a dangerous killer for the female, which seriously threatened women's life, leading to huge pressures to society. The present study assessed the mechanism underlying the involvement of bone marrow tyrosine kinase on chromosome X (BMX) in breast cancer development. METHODS: The expression of BMX was examined by qPCR and immunohistochemistry. The effect of BMX on cell proliferation and migration was detected by Clone formation assay and Transwell assay. In vitro study, the correlation of BMX with Wnt/ß-catenin pathway was explored by western blot and TOP/FOP flash assay. RESULTS: In the present study, we found that BMX was up-regulated in breast cancer, which was associated with the tumor differentiation and TNM stage. Oncogenic BMX enhanced the ability of breast cancer cell proliferation and migration. Furthermore, BMX could up-regulate the protein expression levels of p-ß-catenin (Y142), p-ß-catenin(Y654) and inhibit the expression level of p-ß-catenin (S33/37), thus activating Wnt/ß-catenin pathway in MCF-7 and MDA-MB-231 cells. In addition, we revealed that BMX promoted GSK3ß phosphorylation, which suppressed the degradation of ß-catenin. CONCLUSIONS: In this study, we identified that BMX-activated Wnt/ß-catenin signaling pathway, playing an oncogenic role in breast cancer, suggesting that BMX could become a potential treatment target of breast cancer.

Identification of biomarkers and construction of a microRNA-mRNA regulatory network for ependymoma using integrated bioinformatics analysis.

Ependymomas (EPNs) are one of the most common types of malignant neuroepithelial tumors. In an effort to identify potential biomarkers involved in the pathogenesis of EPN, the mRNA expression profiles of the GSE25604, GSE50161, GSE66354, GSE74195 and GSE86574 datasets, in addition to the microRNA (miRNA/miR) expression profiles of GSE42657 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between EPN and normal brain tissue samples were identified using the Limma package in R and GEO2R, respectively. Functional and pathway enrichment analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction network was constructed using the Search Tool for Retrieval of Interacting Genes database, which was visualized using Cytoscape. The targeted genes of DEMs were predicted using miRWalk2.0 and a miRNA-mRNA regulatory network was constructed. Following analysis, a total of 948 DEGs and 129 DEMs were identified. Functional enrichment analysis revealed that 609 upregulated DEGs were significantly enriched in 'PI3K-Akt signaling pathway', while 339 downregulated DEGs were primarily involved in 'cell junction' and 'retrograde endocannabinoid signaling'. In addition, 6 hub genes [cyclin dependent kinase 1, CD44 molecule (Indian blood group) (CD44), proliferating cell nuclear antigen (PCNA), MYC, synaptotagmin 1 (SYT1) and kinesin family member 4A] and 6 crucial miRNAs [homo sapiens (hsa)-miR-34a-5p, hsa-miR-449a, hsa-miR-106a-5p, hsa-miR-124-3p, hsa-miR-128-3p and hsa-miR-330-3p] were identified as biomarkers and potential therapeutic targets for EPN. Furthermore, a microRNA-mRNA regulatory network was constructed to highlight the interactions between DEMs and their target DEGs; this included the hsa-miR-449a-SYT1, hsa-miR-34a-5p-SYT1, hsa-miR-330-3p-CD44 and hsa-miR-124-3p-PCNA pairs, whose expression levels were confirmed using reverse transcription-quantitative polymerase chain reaction. In conclusion, the present study may provide important data for the investigation of the molecular mechanisms of EPN pathogenesis.

Silencing lncRNA SNHG6 suppresses proliferation and invasion of breast cancer cells through miR-26a/VASP axis.

The important role of LncRNA in the development of breast cancer is attracting more and more attention. In the previous study, we found that the expression level of LncRNA SNHG6 in breast cancer tissues and cells was significantly increased, but its mechanism in the development of breast cancer was still unclear. Our study found that knockdown of SNHG6 significantly inhibited the proliferation, migration and invasion of breast cancer cells MCF-7 and MDA-MB-231 cells. Further study showed that knockdown of SNHG6 significantly inhibited the expression level of VASP. More importantly, SNHG6 and VASP both can bind directly to miR-26a, suggesting that SNHG6 could act as a ceRNA to sponge miR-26a, thereby promoting the expression of VASP, which leading to activated proliferation, migration and invasion of breast cancer cells. Taken together, this study revealed the important role of the SNHG6/miR-26a/VASP regulatory network in the development of breast cancer, and provided a reference for exploring new pathogenesis and biomarkers of breast cancer.

A novel oncogene TRIM63 promotes cell proliferation and migration via activating Wnt/ß-catenin signaling pathway in breast cancer.

The development of breast cancer is still a relatively unclear biological process, and there is currently no consensus on the occurrence of breast cancer and the process of tumor metastases. This study was to reveal a correlation between TRIM63 and the development of breast cancer. In this study, we found that the expression of TRIM63 was significantly increased in breast cancer tissues and closely related to pathological differentiation and TNM stage of breast cancer. Overexpression of TRIM63 could significantly promote proliferation and migration of breast cancer cells, while TRIM63 knockdown significantly inhibited the proliferation and migration of breast cancer cells. In addition, TRIM63 could activate Wnt/ß-catenin signaling pathway in breast cancer cells. Further study found that TRIM63 could regulate ß-catenin degradation by promoting GSK3ß phosphorylation. Our study revealed that TRIM63, as an oncogene, involved in breast cancer progression by activating the Wnt/ß-catenin signaling pathway, suggesting that the potential applicability of TRIM63 as a target for breast cancer treatment.