CircPPAP2B controls metastasis of clear cell renal cell carcinoma via HNRNPC-dependent alternative splicing and targeting the miR-182-5p/CYP1B1 axis.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common malignant tumor worldwide. Metastasis is a leading case of cancer-related deaths of RCC. Circular RNAs (circRNAs), a class of noncoding RNAs, have emerged as important regulators in cancer metastasis. However, the functional effects and regulatory mechanisms of circRNAs on RCC metastasis remain largely unknown. METHODS: High-throughput RNA sequencing techniques were performed to analyze the expression profiles of circRNAs and mRNAs in highly and poorly invasive clear cell renal cell carcinoma (ccRCC) cell lines. Functional experiments were performed to unveil the regulatory role of circPPAP2B in the proliferation and metastatic capabilities of ccRCC cells. RNA pulldown, Mass spectrometry analysis, RNA methylation immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP), next-generation RNA-sequencing and double luciferase experiments were employed to clarify the molecular mechanisms by which circPPAP2B promotes ccRCC metastasis. RESULTS: In this study, we describe a newly identified circular RNA called circPPAP2B, which is overexpressed in highly invasive ccRCC cells, as determined through advanced high-throughput RNA sequencing techniques. Furthermore, we observed elevated circPPAP2B in ccRCC tissues, particularly in metastatic ccRCC tissues, and found it to be associated with poor prognosis. Functional experiments unveiled that circPPAP2B actively stimulates the proliferation and metastatic capabilities of ccRCC cells. Mechanistically, circPPAP2B interacts with HNRNPC in a m6A-dependent manner to facilitate HNRNPC nuclear translocation. Subcellular relocalization was dependent upon nondegradable ubiquitination of HNRNPC and stabilization of an HNRNPC/Vimentin/Importin α7 ternary complex. Moreover, we found that circPPAP2B modulates the interaction between HNRNPC and splicing factors, PTBP1 and HNPNPK, and regulates pre-mRNA alternative splicing. Finally, our studies demonstrate that circPPAP2B functions as a miRNA sponge to directly bind to miR-182-5p and increase CYP1B1 expression in ccRCC. CONCLUSIONS: Collectively, our study provides comprehensive evidence that circPPAP2B promotes proliferation and metastasis of ccRCC via HNRNPC-dependent alternative splicing and miR-182-5p/CYP1B1 axis and highlights circPPAP2B as a potential therapeutic target for ccRCC intervention.

[Digital twin hospitals: transforming the future of healthcare].

Since the concept of digital twin technology has been put forward, after decades of rapid development and wide application, it has not only made great achievements in many fields, but also brought broader prospects for the development of the medical field. As an important trend in the medical industry, digital twin hospitals play multiple roles by connecting physical hospitals and virtual hospitals and benefit the "patient-medical staff-hospital administrators", highlighting the immeasurable promising application of digital twin technology in smart hospitals. This review takes digital twin technology as an entry point, briefly introduces the progress of its application in various fields, focuses on the characteristics of digital twin technology, practical application cases in hospitals and their limitations, and also looks forward to its future development prospects, aiming to provide certain useful insights and guidance for the future of digital twin hospitals, and also expecting it to play an important role in changing the future of healthcare to a certain extent.

XGBoost-based and tumor-immune characterized gene signature for the prediction of metastatic status in breast cancer.

BACKGROUND: For a long time, breast cancer has been a leading cancer diagnosed in women worldwide, and approximately 90% of cancer-related deaths are caused by metastasis. For this reason, finding new biomarkers related to metastasis is an urgent task to predict the metastatic status of breast cancer and provide new therapeutic targets. METHODS: In this research, an efficient model of eXtreme Gradient Boosting (XGBoost) optimized by a grid search algorithm is established to realize auxiliary identification of metastatic breast tumors based on gene expression. Estimated by ten-fold cross-validation, the optimized XGBoost classifier can achieve an overall higher mean AUC of 0.82 compared to other classifiers such as DT, SVM, KNN, LR, and RF. RESULTS: A novel 6-gene signature (SQSTM1, GDF9, LINC01125, PTGS2, GVINP1, and TMEM64) was selected by feature importance ranking and a series of in vitro experiments were conducted to verify the potential role of each biomarker. In general, the effects of SQSTM in tumor cells are assigned as a risk factor, while the effects of the other 5 genes (GDF9, LINC01125, PTGS2, GVINP1, and TMEM64) in immune cells are assigned as protective factors. CONCLUSIONS: Our findings will allow for a more accurate prediction of the metastatic status of breast cancer and will benefit the mining of breast cancer metastasis-related biomarkers.

m6A RNA methylation regulator-based signature for prognostic prediction and its potential immunological role in uterine corpus endometrial carcinoma.

BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) is the most common female pelvic malignancy worldwide. N6-methyladenosine (m6A) plays an important role in various cellular responses, especially in cancer progression. However, the correlation between prognostic UCEC and m6A RNA methylation regulators remains unclear. METHODS: We used The Cancer Genome Atlas (TCGA) to provide a gene signature that could improve the prognostic evaluation of UCEC patients according to the distinct genetic trait of m6A RNA methylation regulators from a bioinformatics perspective. After comparing UCEC subgroups with different genetic profiles of m6A regulators, we identified 71 differentially expressed genes associated with overall survival (OS) and generated a nine-gene signature through least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Finally, we used in vitro and in vivo tumor cell experiments as well as the immune correlation analysis to verify the function of each gene in the proposed gene signature. RESULTS: Time-dependent receiver operating characteristic (ROC) curves revealed that the proposed gene signature could predict the outcome of UCEC patients accurately. We found that CDKN2A mainly acted from the perspective of tumor cells, while COL4A4, PXDN, TIGIT, CHODL, LMO3, KCNJ12, L1CAM, and EPHB1 might play a role in UCEC from an immunological point of view. CONCLUSIONS: From an epigenetics perspective, the m6A RNA methylation regulator-based gene signature can predict the prognosis of UCEC patients and immune therapeutic efficacy.

YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells.

BACKGROUND: Glioma is a common type of malignant brain tumor with a high mortality and relapse rate. The endosomal sorting complex required for transport (ESCRT) has been reported to be involved in tumorigenesis. However, the molecular mechanisms have not been clarified. METHODS: Bioinformatics was used to screen the ESCRT subunits highly expressed in glioma tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The function of the ESCRT subunits in glioma cells was examined in vitro. Transcriptome sequencing analyzed the target genes and signaling pathways affected by the ESCRT subunit. Finally, the relationship between m6A (N6-methyladenosine) modification and high expression of the ESCRT subunit was studied. RESULTS: VPS25 was upregulated in glioma tissues, which was correlated with poor prognosis in glioma patients. Furthermore, VPS25 knockdown inhibited the proliferation, blocked the cell cycle, and promoted apoptosis in glioma cells. Meanwhile, VPS25 induced a G0/G1 phase arrest of the cell cycle in glioma cells by directly mediating p21, CDK2, and cyclin E expression, and JAK-signal transducer and activator of transcription (STAT) activation. Finally, YTHDC1 inhibited glioma proliferation by reducing the expression of VPS25. CONCLUSION: These results suggest that VPS25 is a promising prognostic indicator and a potential therapeutic target for glioma.

Parotitis due to Burkholderia cepacia infection after autologous hematopoietic stem cell transplantation.

Burkholderia cepacia predominantly causes opportunistic infections in hospitalized and immunocompromised patients such as patients with cystic fibrosis, cancer, or human immunodeficiency virus (HIV). Nonetheless, Burkholderia cepacia is infrequently reported to cause infection in hematopoietic stem cell transplantation (HSCT) recipients. Herein, we report a rare case of suppurative parotitis in a 31-year-old patient with T-cell lymphoblastic lymphoma (T-LBL) who underwent auto-HSCT. The secretion from the Stensen duct was collected, and Burkholderia cepacia was detected using the VITEK-2 identification system. Additionally, sensitive antibiotic therapy against this bacterium was also effective. This is the first case of parotitis triggered by Burkholderia cepacia after auto-HSCT, and it is also the first reported domestic case. This case emphasizes the importance of considering bacterial infections in general and Burkholderia cepacia specifically in HSCT patients with post-transplant parotitis.

MHC class IIα polymorphism and its association with resistance/susceptibility to Vibrio harveyi in golden pompano (Trachinotus ovatus).

The major histocompatibility complex (MHC) plays an important role in the vertebrate immune response to antigenic peptides, and it is essential for recognizing foreign pathogens in organisms. In this study, MHC class IIα (Trov-MHC IIα) from the golden pompano (Trachinotus ovatus) was first cloned and identified. The gene structure of Trov-MHC IIα was contained four exons and three introns. High levels of polymorphism were found in the exon 2 of Trov-MHC IIα. A total of 29 different MHC class IIα alleles with high polymorphism were identified from 80 individuals. The ratio of non-synonymous substitutions (dN) to synonymous substitutions (dS) was 3.157 (>1) in the peptide binding regions (PBRs) of Trov-MHC IIα, suggesting positive balancing selection. Six alleles were selected to analyze the association between alleles and resistance/susceptibility to Vibrio harveyi in golden pompano. The results showed that Trov-DAA*6401 and Trov-DAA*6702 alleles were associated with the resistance to V. harveyi in golden pompano, while alleles Trov-DAA*6304 and Trov-DAA*7301 were associated with the susceptibility to V. harveyi in golden pompano. This study confirmed the association between alleles of MHC class IIα and disease resistance, and also detected some alleles which might be correlated with high V. harveyi-resistance. These disease resistance-related MHC alleles could be used as potential genetic markers for molecular marker-assisted selective breeding in the golden pompano.

Interplay between Children's Electronic Media Use and Prosocial Behavior: The Chain Mediating Role of Parent-Child Closeness and Emotion Regulation.

In the contemporary digital milieu, children's pervasive engagement with electronic media is ubiquitous in their daily lives, presenting complex implications for their socialization. Prosocial behavior, a cornerstone of social interaction and child development, is intricately intertwined with these digital experiences. This relation gains further depth, considering the significant roles of parent-child relationships and emotion regulation in shaping children's social trajectories. This study surveyed 701 families to examine the association between children's electronic media use and prosocial behavior, specifically exploring the mediating roles of parent-child closeness and emotion regulation. Structural equation modeling was employed for the analysis. Children's electronic media use negatively correlated with prosocial behavior, parent-child closeness, and emotion regulation. In contrast, a positive association emerged between parent-child closeness, emotion regulation, and prosocial behavior. Emotion regulation also correlated positively with prosocial behavior. Statistical analyses revealed that parent-child closeness and emotion regulation function as both individual and sequential mediators in the relation between electronic media use and prosocial behavior. The study's analyses reveal that fostering children's prosocial behavior in the digital era requires strong family ties, effective emotional management, and balanced digital exposure, which are pivotal for their comprehensive development.

Connections between Parental Phubbing and Electronic Media Use in Young Children: The Mediating Role of Parent-Child Conflict and Moderating Effect of Child Emotion Regulation.

In this digital age, where parental attention is often diverted by digital engagement, the phenomenon of "parental phubbing," defined as parents ignoring their children in favor of mobile devices, is scrutinized for its potential impact on child development. This study, utilizing questionnaire data from 612 parents and Structural Equation Modeling (SEM) with moderated mediation, examines the potential association between parental phubbing and young children's electronic media use. The findings revealed a correlation between parental phubbing and increased electronic media use in children. Parent-child conflict, informed by instances of parental phubbing, was identified as a partial mediator in this relation. Notably, children's emotion regulation emerged as a moderating factor, with adept regulation linked to reduced adverse effects of parental phubbing and improved relational harmony. These findings underscore the importance of parental awareness of their digital behaviors and the benefits of fostering robust parent-child relationships and supporting children's emotional regulation to nurture well-adjusted "digital citizens" in the contemporary media landscape.

The role of EMG1 in lung adenocarcinoma progression: Implications for prognosis and immune cell infiltration.

BACKGROUND AND AIMS: Lung adenocarcinoma (LUAD) is the most common and aggressive cancer with a high incidence. N1-specific pseudouridine methyltransferase (EMG1), a highly conserved nucleolus protein, plays an important role in the biological development of ribosomes. However, the role of EMG1 in the progression of LUAD is still unclear. METHODS: The expression of EMG1 in LUAD cells, and LUAD tissues, and adjacent noncancerous tissues was quantified using real-time polymerase chain reaction (PCR) and western blotting. The roles of EMG1 in LUAD cell proliferation, migration, invasion and tumorigenicity were explored in vitro and in vivo. Western blot analysis to underlying molecular mechanism of EMG1 regulating the biological function of LUAD. EMG1 expression and its impact on tumor prognosis were analyzed using a range of databases including GEPIA, UALCAN, cBioPortal, LinkedOmics, and Kaplan-Meier Plotter. RESULTS: EMG1 expression was elevated in LUAD patients compared to normal tissues, and EMG1 expression was strongly correlated with prognosis in LUAD patients. EMG1 expression correlated with age, gender, N stage, T stage, and pathologic stage. EMG1 expression was strongly positively correlated with MRPL51, PHB2, SNRPG, ATP5MD, and TPI1, and strongly negatively correlated with MACF1, DOCK9, RAPGEF2, SYNJ1, and KIDINS220, the major enrichment pathways for EMG1 and related genes include Cell cycle, DNA Replication and Pathways in cancer signaling pathways. EMG1 expression level was significantly increased in LUAD cell lines and tissues. Knockdown of EMG1 could inhibit LUAD cell proliferation, migration, invasion, and tumorigenicity. Besides, EMG1 overexpression could promote LUAD cell proliferation, migration, and invasion. High expression of EMG1 predicts poor prognosis in LUAD patients, and EMG1 may play an oncogenic role in the tumor microenvironment by participating in the infiltration of LUAD immune cells. CONCLUSIONS: EMG1 regulated various functions in LUAD by directly mediating Akt/mTOR/p70s6k signaling pathways activation. The results suggest that EMG1 may be a novel biomarker for assessing prognosis and immune cell infiltration in LUAD.

Integrative analysis of genomic and epigenomic regulation reveals miRNA mediated tumor heterogeneity and immune evasion in lower grade glioma.

The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.

Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.

Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.

Association between Electronic Media Use and Internalizing Problems: The Mediating Effect of Parent-Child Conflict and Moderating Effect of Children's Age.

In today's digital world, children are exposed extensively to electronic media, making it an integral part of their daily lives. However, excessive use of electronic media during childhood has been associated with various internalizing problems. Moreover, parent-child conflict and children's age may be closely associated with children's problem behaviors. The current study employed a cross-sectional design and conducted a questionnaire survey of 711 parents to examine the association between children's electronic media use and their internalizing problems. Furthermore, this study probed the mediating role of parent-child conflict within this association and the moderating effect of children's age. The results of structural equation modeling showed a positive correlation between children's use of electronic media and their internalizing difficulties. Parent-child conflict served as a mediating factor in this association. Results also showed that the association between parent-child conflict and internalizing problems becomes more pronounced as children grow older. These findings imply that parents should encourage their children to develop healthy habits in using electronic media while fostering positive relationships. Parents should also be mindful of the psychological changes as children age and provide guidance to help them become proficient digital citizens.

Relations between Video Game Engagement and Social Development in Children: The Mediating Role of Executive Function and Age-Related Moderation.

The global proliferation of video games, particularly among children, has led to growing concerns about the potential impact on children's social development. Executive function is a cognitive ability that plays a crucial role in children's social development, but a child's age constrains its development. To examine the association between video game engagement and children's social development while considering the mediating role of executive function and the moderating role of age, a questionnaire was distributed to a sample of 431 parents. The results revealed a negative relation between video game engagement and social development in children, with executive function found to mediate this relation fully. Additionally, the negative association between video game engagement and executive function became more pronounced as children grew older. In light of these findings, it is advisable to adopt proactive strategies to limit excessive video game use, consider the developmental characteristics of children at different ages, and prioritize the promotion of executive function to facilitate social development among children.

m6A-mediated upregulation of LINC01003 regulates cell migration by targeting the CAV1/FAK signaling pathway in glioma.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in the progression of glioma. Here, we examined the potential functions of a lncRNA, LINC01003, in glioma and characterized the underlying molecular mechanisms. METHODS: The GEIPA2 and Chinese Glioma Genome Atlas (CCGA) databases were employed to analyze gene expression and the overall survival curve in patients with glioma. The functions of LINC01003 in glioma growth and migration were assessed by loss-of-function experiments in vitro and in vivo. RNA sequencing was used to determine the signaling pathways effected by LINC01003. Bioinformatics analysis and RNA immunoprecipitation (RIP) assays were used to explore the mechanism underlying the N6-methyladenine (m6A) modification-dependent upregulation of LINC01003 in glioma. RESULTS: LINC01003 expression was upregulated in glioma cell lines and tissues. Higher LINC01003 expression predicted shorter overall survival time in glioma patients. Functionally, LINC01003 knockdown inhibited the cell cycle and cell proliferation and migration in glioma cells. Mechanistically, RNA sequencing revealed that LINC01003 mediated the focal adhesion signaling pathway. Furthermore, LINC01003 upregulation is induced by m6A modification regulated by METTL3. CONCLUSION: This study characterized LINC01003 as a lncRNA that contributes to tumorigenesis in glioma and demonstrated that the LINC01003-CAV1-FAK axis serves as a potential therapeutic target for glioma.

GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A.

GINS1 is a GINS complex subunit that functions along with the MCM2-7 complex and Cdc45 in eukaryotic DNA replication. Despite the significance of the GINS complex in the switch between quiescence and proliferation of glioma cells inside and outside the perinecrotic niche, the biological functions and the underlying mechanism of GINS1 remain unclear. Unlike in normal cells and tissues, GINS1 expression level was significantly upregulated in glioma cells and tissues. High expression of GINS1 predicted an advanced clinical grade and a poor survival. Functional assays revealed that GINS1 aggravated glioma malignant phenotypes in vitro and in vivo. Mechanistically, this study identified that GINS1 physically interacts with TOP2A. GINS1 promotes glioma cell proliferation and migration through USP15-mediated deubiquitination of TOP2A protein. Our results delineate the clinical significance of GINS1 in glioma and the regulatory mechanisms involved in glioma cell proliferation and migration. This work provides potential therapeutic targets for glioma treatment.

Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer.

Introduction: Tumors are usually refractory to anti-cancer therapeutics under hypoxic conditions. However, the underlying molecular mechanism remains to be elucidated. Objectives: Our study intended to identify hypoxia inducible lncRNAs and their biological function in gastric cancer (GC). Methods: Differentially expressed lncRNAs were determined by microarray analysis between GC cells exposed to hypoxia (1% O2) and normoxia (21% O2) for 24 h. The expression level of CBSLR was manipulated in several GC cell lines to perform molecular and biological analyses both in vitro and in vivo. Results: We identified a hypoxia-induced lncRNA-CBSLR that protected GC cells from ferroptosis, leading to chem-resistance. Mechanically, CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of CBS mRNA by enhancing the binding of YTHDF2 with the m6A-modified coding sequence (CDS) of CBS mRNA. Furthermore, under decreased CBS levels, the methylation of the ACSL4 protein was reduced, leading to protein polyubiquitination and degradation of ACSL4. This, in turn, decreased the pro-ferroptosis phosphatidylethanolamine (PE) (18:0/20:4) and PE (18:0/22:4) content and contributed to ferroptosis resistance. Notably, CBSLR is upregulated, whereas CBS is downregulated in GC tissues compared to matched normal tissues; and GC patients with high CBSLR/low CBS levels have a worse clinical outcome and a poorer response to chemotherapy. Conclusion: Our study reveals a novel mechanism in how HIF1α/CBSLR modulates ferroptosis/chemoresistance in GC, illuminating potential therapeutic targets for refractory hypoxic tumors.

Activation of MAT2A-ACSL3 pathway protects cells from ferroptosis in gastric cancer.

BACKGROUND: Ferroptosis, a unique form of nonapoptotic-regulated cell death caused by overwhelming lipid peroxidation, represents an emerging tumor suppression mechanism. Growing evidence has demonstrated that cell metabolism plays an important role in the regulation of ferroptosis. Specifically, the association between methionine metabolism and ferroptosis remains undefined. METHODS: We performed in vitro and in vivo experiments to evaluate the influence of methionine metabolism on ferroptosis sensitivity. Pharmacological and genetic blockade of the methionine cycle was utilized and relevant molecular analyses were performed. RESULTS: We identified MAT2A as a driver of ferroptosis resistance. Mechanistically, MAT2A mediates the production of S-adenosylmethionine (SAM), which upregulates ACSL3 by increasing the trimethylation of lysine-4 on histone H3 (H3K4me3) at the promoter area, resulting in ferroptosis resistance. CONCLUSIONS: Collectively, these results established a link between methionine cycle activity and ferroptosis vulnerability in gastric cancer.

Loss of FAM60A attenuates cell proliferation in glioma via suppression of PI3K/Akt/mTOR signaling pathways.

BACKGROUND: Glioma is a common malignant tumor of the central nervous system with a high incidence and mortality. Family with sequence similarity 60 member A (FAM60A) is a new subunit of the Sin3 deacetylase complex. The clinical significance and biologic role of FAM60A in glioma remain unclear. METHODS: The expression of FAM60A in normal glial cells, glioma cells, and five-paired gliomas, and adjacent noncancerous tissues was quantified using real-time polymerase chain reaction (PCR) and western blotting. FAM60A protein expression in 179 archived, paraffin-embedded glioma samples was analyzed using immunohistochemistry. The roles of FAM60A in glioma cell proliferation and tumorigenicity were explored in vitro and in vivo. The underlying molecular mechanisms were elucidated using Western blot assay. Serum exosomal FAM60A levels of glioma patients were detected using electron microscopy, western blot, and real-time PCR. RESULTS: FAM60A expression was significantly up-regulated in glioma tissues and cell lines and positively associated with a worse outcome in glioma. Knockdown of FAM60A could inhibit glioma cell proliferation and tumorigenicity in vitro and in vivo. Besides, FAM60A expression was detectable in extracted serum exosomes with a higher expression in the glioma cancer group than in the normal group. CONCLUSIONS: Loss of FAM60A attenuates cell proliferation in glioma by suppressing PI3K/Akt/mTOR signaling pathways. Therefore, FAM60A may act as a prognostic biomarker and therapeutic target for glioma.

CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis.

CPVL (carboxypeptidase, vitellogenic-like) is a serine carboxypeptidase that was first characterized in human macrophages. However, the function of CPVL remains unclear in a variety of tumors. The quantitative PCR (qPCR), Western blotting, and IHC assays were utilized to measure the CPVL expression. CPVL was significantly upregulated in glioma cells and tissues compared with normal cells and tissues, respectively. Moreover, high CPVL expression was correlated with advanced clinical grade and poor prognosis. Silencing of CPVL promoted glioma cell apoptosis, and it inhibited cell proliferation and tumorigenicity in vitro and in vivo. Ingenuity Pathway Analysis (IPA) demonstrated that CPVL silencing activated the IFN-γ/STAT1 signaling pathway, thereby inducing glioma cell apoptosis. Mechanistically, immunopurification, mass spectrometry, IP, and glutathione S-transferase (GST) pull-down experiments elucidated that CPVL physically interacts with Bruton's tyrosine kinase (BTK) and downregulates the STAT1 phosphorylation through promoting p300-mediated STAT1 acetylation. Our findings reveal the crucial role of CPVL in promoting the progression of glioma through suppressing STAT1 phosphorylation. CPVL might serve as a potential prognostic biomarker and therapeutic target for the treatment of glioma.