Clinical significance and potential pathogenesis of VCAN in adult non-cystic fibrosis bronchiectasis: a retrospective study.

BACKGROUND: The pathogenesis of adult non-cystic fibrosis (CF) bronchiectasis is complex, and the relevant molecular mechanism remains ambiguous. Versican (VCAN) is a key factor in inflammation through interactions with adhesion molecules. This study constructs a stable panoramic map of mRNA, reveals the possible pathogenesis of bronchiectasis, and provides new ideas and methods for bronchiectasis. METHODS: Peripheral blood and tissue gene expression data from patients with bronchiectasis and normal control were selected by bioinformatics analysis. The expression of VCAN in peripheral blood and bronchial tissues of bronchiectasis were obtained by transcriptome sequencing. The protein expression levels of VCAN in serums were verified by the enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of VCAN in co-culture of Pseudomonas aeruginosa and bronchial epithelial cells were verified by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the biological function of VCAN was detected by the transwell assay. RESULTS: The expression of VCAN was upregulated in the bronchiectasis group by sequencing analysis (P < 0.001). The expression of VCAN in the bronchial epithelial cell line BEAS-2B was increased in P. aeruginosa (P.a), which was co-cultured with BEAS-2B cells (P < 0.05). The concentration of VCAN protein in the serum of patients with bronchiectasis was higher than that in the normal control group (P < 0.05). Transwell experiments showed that exogenous VCAN protein induced the migration of neutrophils (P < 0.0001). CONCLUSIONS: Our findings indicate that VCAN may be involved in the development of bronchiectasis by increasing the migration of neutrophils and play an important role in bronchial pathogenesis.

Catalases mediate tobacco resistance to virus infection through crosstalk between salicylic acid and auxin signaling pathways.

Catalases (CATs) play important roles in plant growth, development and defense responses. Previous studies have shown that CATs exhibit different or even opposite effects on plant immunity in different plant-pathogen interactions, but little is known about the mechanisms. In this study, Nicotiana tabacum plants with overexpression or knockout of CAT genes, tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were employed to investigate the role of CAT in compatible plant-virus interactions. The results showed that there were dynamic changes in the effect of CAT on N. tabacum defense responses. Overexpression of catalase 1 (CAT1) and catalase 3 (CAT3) improved N. tabacum resistance in the early stage of virus infection but depressed it during the late stages of pathogenesis, especially in CAT3 overexpressing plants. The lower level of electrolyte leakage, lower contents of malonaldehyde and hydrogen peroxide (H2 O2 ), higher activities of antioxidant enzymes and improved functions of photosystem II corresponded to the milder symptoms and higher resistance of infected tobacco plants. In addition, the infection of TMV and CMV resulted in expression changes of CATs in tobacco plants, and pretreatment with H2 O2 facilitated TMV and CMV infection. Further experiments showed that the content of salicylic acid (SA) and the expression of genes related to SA signaling pathway were positively correlated with plant resistance, whereas auxin and its related signaling pathway were related to the viral susceptibility of plants. Taken together, our results demonstrated that CAT1 and CAT3 mediated tobacco resistance to virus infection through crosstalk between SA and auxin signaling pathways.

CEP55: an immune-related predictive and prognostic molecular biomarker for multiple cancers.

BACKGROUND: Centrosomal protein 55 (CEP55) plays a significant role in specific cancers. However, comprehensive research on CEP55 is lacking in pan-cancer. METHODS: In-house and multi-center samples (n = 15,823) were used to analyze CEP55 in 33 cancers. The variance of CEP55 expression levels among tumor and control groups was evaluated by the Wilcoxon rank-sum test and standardized mean difference (SMD). The clinical value of CEP55 in cancers was assessed using receiver operating characteristic (ROC) curves, Cox regression analysis, and Kaplan-Meier curves. The correlations between CEP55 expression and the immune microenvironment were explored using Spearman's correlation coefficient. RESULTS: The data of clustered regularly interspaced short palindromic repeats confirmed that CEP55 was essential for the survival of cancer cells in multiple cancer types. Elevated CEP55 mRNA expression was observed in 20 cancers, including glioblastoma multiforme (p < 0.05). CEP55 mRNA expression made it feasible to distinguish 21 cancer types between cancer specimens and their control samples (AUC = 0.97), indicating the potential of CEP55 for predicting cancer status. Overexpression of CEP55 was correlated with the prognosis of cancer individuals for 18 cancer types, exhibiting its prognostic value. CEP55 expression was relevant to tumor mutation burden, microsatellite instability, neoantigen counts, and the immune microenvironment in various cancers (p < 0.05). The expression level and clinical relevance of CEP55 in cancers were verified in lung squamous cell carcinoma using in-house and multi-center samples (SMD = 4.07; AUC > 0.95; p < 0.05). CONCLUSION: CEP55 may be an immune-related predictive and prognostic marker for multiple cancers, including lung squamous cell carcinoma.

Molecular Dynamics Study of the Curvature-Driven Interactions between Carbon-Based Nanoparticles and Amino Acids.

We researched the interaction between six representative carbon-based nanoparticles (CBNs) and 20 standard amino acids through all-atom molecular dynamics simulations. The six carbon-based nanoparticles are fullerene(C60), CNT55L3, CNT1010L3, CNT1515L3, CNT2020L3, and two-dimensional graphene (graphene33). Their curvatures decrease sequentially, and all of the CNTs are single-walled carbon nanotubes. We observed that as the curvature of CBNs decreases, the adsorption effect of the 20 amino acids with them has an increasing trend. In addition, we also used multi-dimensional clustering to analyze the adsorption effects of 20 amino acids on six carbon-based nanoparticles. We observed that the π-π interaction still plays an extremely important role in the adsorption of amino acids on carbon-based nanoparticles. Individual long-chain amino acids and "Benzene-like" Pro also have a strong adsorption effect on carbon-based nanoparticles.

Post-transcriptional regulation of α7 nAChR expression by miR-98-5p modulates cognition and neuroinflammation in an animal model of Alzheimer's disease.

Alzheimer's disease (AD) is a complicated neurodegenerative disease and therefore addressing multiple targets simultaneously has been believed as a promising therapeutic strategy against AD. α7 nicotinic acetylcholine receptor (nAChR), which plays an important role in improving cognitive function and alleviating neuroinflammation in central nervous system (CNS), has been regarded as a potential target in the treatment of AD. However, the regulation of α7 nAChR at post-transcriptional level in mammalian brain remains largely speculated. Herein, we uncovered a novel post-transcriptional regulatory mechanism of α7 nAChR expression in AD and further demonstrated that miR-98-5p suppressed α7 nAChR expression through directly binding to the 3'UTR of mRNA. Knockdown of miR-98-5p activated Ca2+ signaling pathway and consequently reversed cognitive deficits and Aß burden in APP/PS1 mice. Furthermore, miR-98-5p downregulation increased α7 nAChR expression, and ameliorated neuroinflammation via inhibiting NF-κB pathway and upregulating Nrf2 target genes. Our findings illustrate a prominent regulatory role of miR-98-5p in targeting inflammation and cognition, and provide an insight into the potential of miR-98-5p/α7 nAChR axis as a novel therapeutic strategy for AD.

Inverse Boltzmann Iterative Multi-Scale Molecular Dynamics Study between Carbon Nanotubes and Amino Acids.

Our work uses Iterative Boltzmann Inversion (IBI) to study the coarse-grained interaction between 20 amino acids and the representative carbon nanotube CNT55L3. IBI is a multi-scale simulation method that has attracted the attention of many researchers in recent years. It can effectively modify the coarse-grained model derived from the Potential of Mean Force (PMF). IBI is based on the distribution result obtained by All-Atom molecular dynamics simulation; that is, the target distribution function and the PMF potential energy are extracted, and then, the initial potential energy extracted by the PMF is used to perform simulation iterations using IBI. Our research results have been through more than 100 iterations, and finally, the distribution obtained by coarse-grained molecular simulation (CGMD) can effectively overlap with the results of all-atom molecular dynamics simulation (AAMD). In addition, our work lays the foundation for the study of force fields for the simulation of the coarse-graining of super-large proteins and other important nanoparticles.

Computational investigation of the binding of a designed peptide to λ light chain amyloid fibril.

Systemic light chain amyloidosis (AL) causes a malignant pathology associated with the formation of amyloid fibrils that deposit in human organs and tissues, leading to dysfunction and severe morbidity. Amyloid fibril-reactive antibodies have been used to remove amyloid from organs and are effective in restoring organ function in patients with AL amyloidosis. Unfortunately, antibodies do not bind amyloid in all AL patients, nor do they efficiently bind many other forms of amyloid. Recently, a synthetic peptide P62 was developed, which binds many forms of systemic amyloidosis and can be further modified and fused to a high-affinity peptide epitope to expand its utility as a novel amyloid immunotherapeutic. However, the molecular-level details of P62-fibril binding mechanisms, critical for future peptide design, are unclear. Here, we combine protein docking, all-atom molecular dynamics simulation and umbrella sampling to study the dynamical interactions between peptide P62 and a structural model of the λ light chain in systemic amyloidosis. We found that P62 only binds to the canonical interface of the fibril where the peptide inserts into the fibril groove and its two termini are more mobile than the helix core. Our results also revealed an important role of the lysine residues of P62 in the binding process by forming initial contacts with aspartic acids on the fibril surface. Collectively, our computational study provided molecular-level insights into the binding mechanism between an amyloid fibril model and peptide P62, which could lay a foundation for rational design of peptides for improved amyloid diagnosis and immunotherapy.

Chilli veinal mottle virus HCPro interacts with catalase to facilitate virus infection in Nicotiana tabacum.

Plant symptoms are derived from specific interactions between virus and host components. However, little is known about viral or host factors that participate in the establishment of systemic necrosis. Here, we showed that helper component proteinase (HCPro), encoded by Chilli veinal mottle virus (ChiVMV), could directly interact with catalase 1 (CAT1) and catalase 3 (CAT3) in the cytoplasm of tobacco (Nicotiana tabacum) plants to facilitate viral infection. In vitro, the activities of CAT1 and CAT3 were inhibited by the interaction between HCPro and CATs. The C-terminus of HCPro was essential for their interaction and was also required for the decrease of enzyme activities. Interestingly, the mRNA and protein level of CATs were up-regulated in tobacco plants in response to ChiVMV infection. Nicotiana tabacum plants with HCPro overexpression or CAT1 knockout were more susceptible to ChiVMV infection, which was similar to the case of H2O2-pre-treated plants, and the overexpression of CAT1 inhibited ChiVMV accumulation. Also, neither CAT1 nor CAT3 could affect the RNA silencing suppression (RSS) activity of HCPro. Our results showed that the interaction between HCPro and CATs promoted the development of plant systemic necrosis, revealing a novel role for HCPro in virus infection and pathogenicity.

Integration of Metabolomics and Transcriptomics To Reveal Metabolic Characteristics and Key Targets Associated with Cisplatin Resistance in Nonsmall Cell Lung Cancer.

Continuous exposure to cisplatin can induce drug resistance to limit efficacy; however, the underlying mechanisms correlated with cisplatin resistance are still unclear. Drug-sensitive A549 cells and cisplatin-resistant A549/DDP cells were used to explore the potential metabolic pathways and key targets associated with cisplatin resistance by integrating untargeted metabolomics with transcriptomics. Data are available via ProteomeXchange with identifier PXD013265. The results of comprehensive analyses showed that 19 metabolites were significantly changed in A549/DDP versus A549 cells, and some pathways had a close relationship with cisplatin resistance, such as the biosynthesis of aminoacyl-tRNA, glycerophospholipid metabolism, and glutathione metabolism. Moreover, transcriptomics analysis showed that the glutathione metabolism was also obviously affected in A549/DDP, which indicated that the glutathione metabolism played an important role in the process of drug resistance. Meanwhile, transcriptomics analysis suggested the four enzymes related to glutathione metabolism-CD13, GPX4, RRM2B, and OPLAH-as potential targets of cisplatin resistance in nonsmall cell lung cancer. Further studies identified the overexpression of these four enzymes in A549/DDP. The elucidation of mechanism and discovery of new potential targets may help us have a better understanding of cisplatin resistance.

Evaluating the role of RAD52 and its interactors as novel potential molecular targets for hepatocellular carcinoma.

BACKGROUND: Radiation sensitive 52 (RAD52) is an important protein that mediates DNA repair in tumors. However, little is known about the impact of RAD52 on hepatocellular carcinoma (HCC). We investigated the expression of RAD52 and its values in HCC. Some proteins that might be coordinated with RAD52 in HCC were also analyzed. METHODS: Global RAD52 mRNA levels in HCC were assessed using The Cancer Genome Atlas (TCGA) database. RAD52 expression was analyzed in 70 HCC tissues and adjacent tissues by quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry. The effect of over-expressed RAD52 in Huh7 HCC cells was investigated. The String database was then used to perform enrichment and functional analysis of RAD52 and its interactome. Cytoscape software was used to create a protein-protein interaction network. Molecular interaction studies with RAD52 and its interactome were performed using the molecular docking tools in Hex8.0.0. Finally, these DNA repair proteins, which interact with RAD52, were also analyzed using the TCGA dataset and were detected by qRT-PCR. Based on the TCGA database, algorithms combining ROC between RAD52 and RAD52 interactors were used to diagnose HCC by binary logistic regression. RESULTS: In TCGA, upregulated RAD52 related to gender was obtained in HCC. The area under the receiver operating characteristic curve (AUC) of RAD52 was 0.704. The results of overall survival (OS) and recurrence-free survival (RFS) indicated no difference in the prognosis between patients with high and low RAD52 gene expression. We validated that RAD52 expression was increased at the mRNA and protein levels in Chinese HCC tissues compared with adjacent tissues. Higher RAD52 was associated with older age, without correlation with other clinicopathological factors. In vitro, over-expressed RAD52 significantly promoted the proliferation and migration of Huh7 cells. Furthermore, RAD52 interactors (radiation sensitive 51, RAD51; X-ray repair cross complementing 6, XRCC6; Cofilin, CFL1) were also increased in HCC and participated in some biological processes with RAD52. Protein structure analysis showed that RAD52-RAD51 had the firmest binding structure with the lowest E-total energy (- 1120.5 kcal/mol) among the RAD52-RAD51, RAD52-CFL1, and RAD52-XRCC6 complexes. An algorithm combining ROC between RAD52 and its interactome indicated a greater specificity and sensitivity for HCC screening. CONCLUSIONS: Overall, our study suggested that RAD52 plays a vital role in HCC pathogenesis and serves as a potential molecular target for HCC diagnosis and treatment. This study's findings regarding the multigene prediction and diagnosis of HCC are valuable.

Localized primary malignant pericardial mesothelioma.

Primary malignant pericardial mesothelioma (PMPM) is an extremely rare tumor, which may appear as a localized or a diffuse mass encasing the heart. Diffuse PMPMs have a poor prognosis due to the difficulty of surgical excision, whereas localized PMPMs have clear margins, thus facilitating surgical excision. Timely diagnosis and proper treatment are crucial for a favorable prognosis. Eight cases of localized PMPMs have been reported so far, but their characteristics have not been fully described. Herein, we present a patient with localized PMPM and describe the diagnosis methods, treatment, and outcomes of these tumors.

Right-sided infective endocarditis with coronary sinus vegetation.

BACKGROUND: Infective endocarditis (IE) is a rare disease with high mortality. Right-sided IE accounts for 5-10% of cases of IE. The tricuspid valve is most commonly affected, oppositely in coronary sinus (CS). The diagnoses, treatments and outcomes of CS vegetation has not been summarized yet. CASE PRESENTATION: We present a 71-year-old man complained of cough and fever. Transthoracic echocardiography revealed the aneurysmal dilated CS with the band medium-echo mobile structure. A sinus venosus atrial septal defect has been detected. He had a persistent left superior vena cava which drained the right atrium via the aneurysmal dilated CS. Blood cultures were positive for Staphylococcus aureus. After intravenous antibiotic therapy, he had the symptom of dyspnea. The suspicious diagnosis is recurrent septic lung emboli which was confirmed by thoracic contrast enhanced computed tomography. The thoracotomy was performed to repair the atrial septum and remove the CS vegetation. Ten days later, the patient was discharged with only mild cough. CONCLUSION: Both positive blood cultures and echocardiography are major criteria in right-sided IE with CS vegetation. Current treatment options of CS vegetation include medical therapy and surgery. The surgical strategy for CS vegetation should be individualized, due to the controversial indications and optimum time of surgery. Most people have a good prognosis after proper treatment.

Unusual Coronary Sinus Tumor in a Pregnant Woman.

Primary coronary sinus tumors are extremely rare. Herein, we present a case of a pregnant woman with a primary myxoma in the coronary sinus (CS), which was diagnosed by echocardiography and computed tomography. We reviewed the literature and found two other primary CS tumors. We summarized the gender, ages, symptoms, diagnostic methods, associated anomalies, treatments, histologic findings, and outcomes of the 3 cases. Dyspnea was a common symptom of all 3 patients. Diagnostic methods included echocardiography, computed tomography, magnetic resonance imaging, and coronary angiography. Associated anomalies included coronary artery fistulas, coronary sinus orifice atresia with persistent left superior vena cava, intra-cardiac invasion, and pericardial effusion. The 3 histologic types of primary CS tumor were haemangioma, lymphoma, and myxoma. The 3 patients received proper treatment and had good therapeutic outcomes.

The 'whole landscape' of research on systemic sclerosis over the past 73 years.

OBJECTIVE: This study aimed to analyse existing research on systemic sclerosis (SSc) conducted over the past 73 years to develop an essential reference for a comprehensive and objective understanding of this field of inquiry. METHODS: Using the Web of Science Core Collection, PubMed, and Scopus databases as data sources for the bibliometric analysis, we searched for published literature related to SSc over the past 73 years. The Bibliometrix package was used to analyse key bibliometric indicators, such as annual publication volume, countries, journals, author contributions, and research hotspots. RESULTS: From 1970 to 2022, the number of SSc articles steadily increased, reaching its peak in 2020-2022, with approximately 1200 papers published in each of these three years. Matucci-Cerinic et al.'s team published the most articles (425). The United States (11,282), Italy (7027), and France (5226) were the most predominant contexts. The most influential scholars in the field were Denton, Leroy, Steen, and Khanna, with H-indices of 86, 84, and 83, respectively. Arthritis and Rheumatism was the most influential journal in this field (H-index 142). High-frequency keywords in the SSc field included fibrosis (738), inflammation (242), vasculopathy (145), fibroblasts (120), and autoantibodies (118) with respect to pathogenesis, and interstitial lung disease (ILD, 708), pulmonary arterial hypertension (PAH, 696), and Raynaud's phenomenon (326) with regards to clinical manifestations. CONCLUSION: In the past three years, SSc research has entered a period of rapid development, mainly driven by research institutions in Europe and the United States. The most influential journal has been Arthritis and Rheumatism, and autoimmune aspects, vasculopathy, fibrogenesis, PAH, and ILD remain the focus of current research and indicate trends in future research.

Explosion of research on psychopathology and social media use after COVID-19: A scientometric study.

BACKGROUND: Despite advances in research on psychopathology and social media use, no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus disease 2019 (COVID-19) outbreak. AIM: To explore the status of research on psychopathology and social media use before and after the COVID-19 outbreak. METHODS: We used Bibliometrix (an R software package) to conduct a scientometric analysis of 4588 relevant studies drawn from the Web of Science Core Collection, PubMed, and Scopus databases. RESULTS: Such research output was scarce before COVID-19, but exploded after the pandemic with the publication of a number of high-impact articles. Key authors and institutions, located primarily in developed countries, maintained their core positions, largely uninfluenced by COVID-19; however, research production and collaboration in developing countries increased significantly after COVID-19. Through the analysis of keywords, we identified commonly used methods in this field, together with specific populations, psychopathological conditions, and clinical treatments. Researchers have devoted increasing attention to gender differences in psychopathological states and linked COVID-19 strongly to depression, with depression detection becoming a new trend. Developments in research on psychopathology and social media use are unbalanced and uncoordinated across countries/regions, and more in-depth clinical studies should be conducted in the future. CONCLUSION: After COVID-19, there was an increased level of concern about mental health issues and a changing emphasis on social media use and the impact of public health emergencies.

Clinical significance and prospective mechanism of increased CDKN2A expression in small cell lung cancer.

BACKGROUND: Although it has been shown that cyclin dependent kinase inhibitor 2A (CDKN2A) plays a significant role in a number of malignancies, its clinicopathological value and function in small cell lung cancer (SCLC) is unclear and warrants additional research. METHODS: The clinical significance of CDKN2A expression in SCLC was examined by multiple methods, including comprehensive integration of mRNA level by high throughput data, Kaplan-Meier survival analysis for prognostic value, and validation of its protein expression using in-house immunohistochemistry. RESULTS: The expression of CDKN2A mRNA in 357 cases of SCLC was evidently higher than that in the control group (n = 525) combing the data from 20 research centers worldwide. The standardized mean difference (SMD) was 3.07, and the area under the curve (AUC) of summary receiver operating characteristic curve (sROC) was 0.97 for the overexpression of CDKN2A. ACC, COAD, KICH, KIRC, PCPG, PRAD, UCEC, UVM patients with higher CDKN2A expression had considerably worse overall survival rates than those with lower CDKN2A expression with the hazard ratio (HR) > 1. CONCLUSION: CDKN2A upregulation extensively enhances the carcinogenesis and progression of SCLC.

A novel prognostic signature of coagulation-related genes leveraged by machine learning algorithms for lung squamous cell carcinoma.

Coagulation-related genes (CRGs) have been demonstrated to be essential for the development of certain tumors; however, little is known about CRGs in lung squamous cell carcinoma (LUSC). In this study, we adopted CRGs to construct a coagulation-related gene prognostic signature (CRGPS) using machine learning algorithms. Using a set of 92 machine learning integrated algorithms, the CRGPS was determined to be the optimal prognostic signature (median C-index = 0.600) for predicting the prognosis of an LUSC patient. The CRGPS was not only superior to traditional clinical parameters (e.g., T stage, age, and gender) and its commutative genes but also outperformed 19 preexisting prognostic signatures for LUSC on predictive accuracy. The CRGPS score was positively correlated with poor prognoses in patients with LUSC (hazard ratio > 1, p < 0.05), indicating its suitability as a prognostic marker for this disease. The CRGPS was observed to be inversely correlated with the degree of infiltration of natural killer cells. For some tumors, patients with lower CRGPS scores are more likely to experience enhanced immunotherapy effects (area under the curve = 0.70), which implies that the CRGPS can potentially predict immunotherapy efficacy. A high CRGPS score is predictive of an LUSC patient being sensitive to several drugs. Collectively, these findings indicate that the CRGPS may be a reliable indicator of the prognoses of patients with LUSC and may be useful for the clinical management of such patients.

The upregulation and transcriptional regulatory mechanisms of Extra spindle pole bodies like 1 in bladder cancer: An immunohistochemistry and high-throughput screening Evaluation.

Background: This study aimed to explore the expression level and transcriptional regulation mechanism of Extra Spindle Pole Bodies Like 1 (ESPL1) in bladder cancer (BC). Methods: A multicentre database of samples (n = 1391) was assayed for ESPL1 mRNA expression in BC and validated at the protein level by immunohistochemical (IHC) staining of in-house samples (n = 202). Single-cell sequencing (scRNA-seq) analysis and enrichment analysis explored ESPL1 distribution and their accompanying molecular mechanisms. ATAC-seq, ChIP-seq and Hi-C data from multiple platforms were used to investigate ESPL1 upstream transcription factors (TFs) and potential epigenetic regulatory mechanisms. Immune-related analysis, drug sensitivity and molecular docking of ESPL1 were also calculated. Furthermore, upstream microRNAs and the binding sites of ESPL1 were predicted. The expression level and early screening efficacy of miR-299-5p in blood (n = 6625) and tissues (n = 537) were examined. Results: ESPL1 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 0.75; 95 % CI = 0.09, 1.40), and IHC staining of in-house samples verified this finding (p < 0.0001). ESPL1 was predominantly distributed in BC epithelial cells. Coexpressed genes of ESPL1 were enriched in cell cycle-related signalling pathways, and ESPL1 might be involved in the communication between epithelial and residual cells in the Hippo, ErbB, PI3K-Akt and Ras signalling pathways. Three TFs (H2AZ, IRF5 and HIF1A) were detected upstream of ESPL1 and presence of promoter-super enhancer and promoter-typical enhancer loops. ESPL1 expression was correlated with various immune cell infiltration levels. ESPL1 expression might promote BC growth and affect the sensitivity and therapeutic efficacy of paclitaxel and gemcitabine in BC patients. As an upstream regulator of ESPL1, miR-299-5p expression was downregulated in both the blood and tissues, possessing great potential for early screening. Conclusions: ESPL1 expression was upregulated in BC and was mainly distributed in epithelial cells. Elevated ESPL1 expression was associated with TFs at the upstream transcription start site (TSS) and distant chromatin loops of regulatory elements. ESPL1 might be an immune-related predictive and diagnostic marker for BC, and the overexpression of ESPL1 played a cancer-promoting role and affected BC patients' sensitivity to drug therapy. miR-299-5p was downregulated in BC blood and tissues and was also expected to be a novel marker for early screening.

FOXS1 promotes prostate cancer progression through the Hedgehog/Gli1 pathway.

BACKGROUND: Prostate cancer (PCa) remains the most common malignant tumor in men, and the clinical treatment still faces many challenges. Several molecular biomarkers of PCa progression have been reported, however, whether FOXS1 can serve as a new biomarker in PCa remains unknown. METHODS: FOXS1 and Gli1 expression was assessed by RT-qPCR and western blot. The binding and regulation roles between FOXS1 and Gli1 were confirmed by Co-IP and ubiquitination assays. Cell viability, proliferation, apoptosis, migration, invasion and EMT progress were assessed through CCK-8, colony formation, flow cytometry, wound-healing, transwell and western blot assays, respectively. In vivo nude mice tumorigenesis model was also conducted to verify PCa growth. RESULTS: FOXS1 was upregulated in the PCa TCGA dataset and cells. High FOXS1 level was correlated with PCa patients' worse tumor stage and shorter survival. FOXS1 knockdown inhibited PCa cell proliferation, invasion, migration, EMT and tumor growth while increased cell apoptosis. Furthermore, FOXS1 knockdown decreased the inactivation of Hedgehog (Hh) pathway. FOXS1 bind to Gli1 and decreased the ubiquitination of Gli1, which resulted in the upregulation of Gli1. Besides, both Gil1 overexpression and Hh signal activation reversed the suppression function of FOXS1 silencing on PCa growth and metastasis. CONCLUSION: FOXS1 bind and stabilized Gli1 by blocking Gli1 ubiquitination, thereby activating Hh signaling to promote PCa cell growth and metastasis.

Clinicopathological and prognostic significance of XPO1 in solid tumors: meta-analysis and TCGA analysis.

INTRODUCTION: Exportin 1 (XPO1) is overexpressed in several solid tumors, and is associated with poor prognosis. Here, we aimed to evaluate the implication of XPO1 expression in solid tumors through a meta-analysis. METHODS: PubMed, Web of Science, and Embase databases were searched for articles published until February 2023. Statistical data of the patients, odds ratios and hazard ratios (HRs), together with their corresponding 95% confidence intervals (CIs) were pooled to assess clinicopathological features and survival outcomes. Besides, the Cancer Genome Atlas (TCGA) was used to explore the prognostic significance of XPO1 in solid tumors. RESULTS: A total of 22 works, comprising 2595 patients were included in this study. The results suggested that increased XPO1 expression was associated with a higher tumor grade, more lymph node metastasis, advanced tumor stage, and progressively worse total clinical stage. Additionally, high XPO1 expression was associated with worse overall survival (OS) (HR = 1.43, 95% CI = 1.12-1.81, P = 0.004) and shorter progression-free survival (HR = 1.40, 95% CI = 1.07-1.84, P = 0.01). An analysis using the TCGA dataset showed that high XPO1 expression was associated with poor OS and disease-free survival. CONCLUSIONS: XPO1 is a promising prognostic biomarker and may constitute a therapeutic target for solid tumors.PROSPERO registration number: CRD42023399159.