The published article titled“MicroRNA-133b Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.
Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postn...Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo.展开更多
Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates...Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates dextran sulfate sodium(DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions.However,the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear.This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.Methods A total of 6021-day-old weaned female piglets were randomly assigned into three groups based on weight:the control group(basal diet with physiological saline gavage),the DSS group(basal diet with 5%DSS gavage),and the DSS+LA group(2%lactate diet with 5%DSS gavage).There were 10 replicates per treatment,with 2 piglets per replicate.Jejunal morphology was assessed via hematoxylin and eosin staining,while Western blotting quantified the protein levels of proliferation markers,including cluster of differentiation 24(CD24),cyclin D1,and wingless/integrated(Wnt)/β-catenin signaling components.In vitro,0.08%DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2(IPEC-J2)cells(n=4)were assessed for viability(Cell Counting Kit-8 assay),apoptosis(flow cytometry),and proliferation parameters,including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5+)stem cell quantification.Results In vivo,DSS administration induced jejunal villus shortening(P<0.05),downregulated protein levels of CD24,cyclin D1,casein kinase 1(CK1),and dishevelled-2(DVL2)(P<0.05).In vitro,DSS promoted apoptosis,inhibited proliferation,diminished the Lgr5+cell populations(P<0.05),and reduced S-phase cell proportions(P<0.05).Conversely,lactate supplementation ameliorated DSS-induced villus atrophy(P<0.05),restored CD24,cyclin D1,CK1,and DVL2 protein levels(P<0.05).Furthermore,in vitro,sodium lactate attenuated DSS-induced apoptosis(P<0.05),enhanced IPEC-J2 proliferation(P<0.05),expanded Lgr5+cells(P<0.05),and increased S-phase progression(P<0.05).Conclusions In summary,lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis.This study provides novel mechanistic evidence supporting lactate's therapeutic potential for IBD management.展开更多
Oncology Research Editorial Office Published:23 March 2026 The published article titled“MicroRNA 125a-5p Inhibits Cell Proliferation and Induces Apoptosis in Hepatitis B Virus-Related Hepatocellular Carcinoma by Down...Oncology Research Editorial Office Published:23 March 2026 The published article titled“MicroRNA 125a-5p Inhibits Cell Proliferation and Induces Apoptosis in Hepatitis B Virus-Related Hepatocellular Carcinoma by Downregulation of ErbB3”has been retracted from Oncology Research,Vol.27,No.4,2019,pp.449-458.DOI:10.3727/096504017X15016337254623 URL:https://www.techscience.com/or/v27n4/48558.展开更多
Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strateg...Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.展开更多
Myostatin(MSTN)is principally expressed in skeletal muscle and negatively regulates muscle growth and development.MSTN mutation can induce muscle overgrowth in cattle by activating cell proliferation,presenting a“dou...Myostatin(MSTN)is principally expressed in skeletal muscle and negatively regulates muscle growth and development.MSTN mutation can induce muscle overgrowth in cattle by activating cell proliferation,presenting a“double-muscle”phenotype.However,the specific regulatory mechanism is still unclear.Here,we found that Ca^(2+)content in muscle tissue and muscle satellite cells of MSTN mutated(MSTN^(–/–))cattle were significantly increased compared to wild-type(WT).Furthermore,transcriptome analysis of muscle satellite cells revealed that TRPC4 was significantly increased in MSTN^(–/–)cattle.And the expression of TRPC4 in muscle tissue of MSTN^(–/–)cattle was detected by RT-qPCR and Western blot,which was significantly higher than that of WT.These results suggested that MSTN mutation promoted muscle satellite cells proliferation through activation of TRPC4 channel.To further verify,ML204,a specific inhibitor of TRPC4,was used to treat MSTN^(–/–)muscle satellite cells.We found that cell proliferation was inhibited,calcineurin expression was downregulated,and the entry of NFATc3 into nuclei was reduced,which was similar to WT group.Thus,MSTN mutation leads to the activation of TRPC4 channel,which increases intracellular Ca^(2+)content,further activates calcineurin/NFATc3 pathway,and ultimately promotes the proliferation of muscle satellite cells.展开更多
Objectives:Tumor recurrence is a major determinant of poor prognosis in hepatocellular carcinoma(HCC),yet its cellular and molecular basis remains incompletely understood.This study aimed to identify recurrenceassocia...Objectives:Tumor recurrence is a major determinant of poor prognosis in hepatocellular carcinoma(HCC),yet its cellular and molecular basis remains incompletely understood.This study aimed to identify recurrenceassociated genes at single-cell resolution and to develop a prognostic model for predicting survival outcomes and immunotherapy responsiveness in HCC.Methods:Single-cell RNA sequencing data from 12 primary and 6 recurrent HCC samples were integrated and analyzed to identify genes characteristic of recurrence.After quality control,principal component analysis,and t-SNE-based clustering were used to identify highly variable genes for cell clustering and annotation.Based on macrophage characteristic genes,a recurrence-related risk score was constructed using a LASSOCox regression model,and a nomogram integrating clinical variables was developed.Prognostic performance was assessed using Kaplan-Meier analysis and time-dependent ROC curves.Immune infiltration profiling was performed to compare immune characteristics between risk groups defined by the prognostic model.Multivariate Cox regression was applied to identify independent prognostic biomarkers,which were subsequently validated by cell function experiments.Results:The risk model effectively stratified patients into high-and low-risk groups with distinct survival outcomes,demonstrating high predictive accuracy for 1-,3-,and 5-year survival.High-risk patients showed altered immune profiles and a reduced predicted response to immunotherapy.GRID2,RNF186,and SLC4A10 were identified as independent prognostic genes,with RNF186 promoting HCC cell proliferation in a SESN2-dependent manner.Conclusion:This prognostic model provides new insights into precision medicine and immunotherapy for HCC,highlighting the potential clinical significance of RNF186 as a therapeutic target.展开更多
Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study ai...Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study aims to identify a novel small molecule,synthesized via proteolysis-targeting chimeras(PROTACs),capable of degrading BCL6,thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.Methods:The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas(TCGA)database and the Human Protein Atlas.Western blotting assays confirmed BCL6 expression in tumor cell lines,leading to the identification of the small molecule compound DZ-865B.To evaluate DZ-865B’s in vitro efficacy,multiple assays were performed,including protein immunoblotting,immunofluorescence,reverse transcription quantitative PCR,EDU proliferation,and soft agar cloning assays.Results:TCGA analysis revealed significant overexpression of BCL6 in DLBCL(p<0.05),corroborated by immunohistological staining and western blotting.DZ-865B induced BCL6 degradation in DLBCL cell lines(OCI-LY-1 and SU-DHL-4)in a concentration-and time-dependent manner,and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway.Notably,DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression,leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis,effectively suppressing DLBCL cell growth.Conclusion:This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells,promoting apoptosis and inhibiting cellular proliferation.These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.展开更多
Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration vi...Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.展开更多
Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.How...Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.展开更多
To explore the potential utilization of Elaeagnus mollis,we conducted a comprehensive assessment of its phytochemical composition,antioxidant properties,cholinesterase inhibition,and anti-HepG2 cell proliferation acti...To explore the potential utilization of Elaeagnus mollis,we conducted a comprehensive assessment of its phytochemical composition,antioxidant properties,cholinesterase inhibition,and anti-HepG2 cell proliferation activity across different plant parts(branch wood,branch bark,and pericarp)using various solvents(water,methanol,ethanol,and n-hexane).Our findings revealed that water extracts displayed superior antioxidant activities in ABTS and RP assays,while methanol extracts exhibited better performance in DPPH and FRAP assays.Moreover,methanol extracts demonstrated the highest effectiveness against anti-HepG2 cell proliferation,whereas n-hexane extracts showed greater efficiency in cholinesterase inhibition.Notably,branch bark extracts exhibited the highest levels of phytochemical compounds,with both branch bark and pericarp extracts demonstrating significant effects in cholinesterase inhibition and anti-HepG2 cell proliferation.Correlation analysis indicated that phytochemical compounds were primarily responsible for the observed biological activities.Overall,extracts from the branch bark and pericarp of E.mollis showed promising potential for antioxidant and anticancer activities,suggesting their suitability for applications in the pharmaceutical industry as health-promoting products.展开更多
Somatic cell nuclear transfer(SCNT)has been successfully employed across various mammalian species,yet cloned animals consistently exhibit low pregnancy rates,primarily due to placental abnormalities such as hyperplas...Somatic cell nuclear transfer(SCNT)has been successfully employed across various mammalian species,yet cloned animals consistently exhibit low pregnancy rates,primarily due to placental abnormalities such as hyperplasia and hypertrophy.This study investigated the involvement of the Hippo signaling pathway in aberrant placentaldevelopmentinSCNT-inducedbovine pregnancies.SCNT-derived cattle exhibited placental hypertrophy,including enlarged abdominal circumference and altered placental cotyledon morphology.RNA sequencing analysis indicated significant dysregulation of Hippo signaling pathway genes in SCNT placentas.Coexpression of YAP1 and CCND1 was observed in cloned blastocysts,placental tissues,and bovine placental mesenchymal stem cells(bPMSCs).Manipulation of YAP1expression demonstrated the capacity to regulate bPMSC proliferation.Experimental assays confirmed the direct binding of YAP1 to CCND1,which subsequently promoted CCND1 expression in bPMSCs.Furthermore,inhibition of CDK6,a downstream target of CCND1,attenuated SCNT bPMSC proliferation.This study identified YAP1 as a key regulatory component within the Hippo signaling pathway that drives placental hyperplasia in cloned cattle through up-regulation of CCND1-CDK6 expression,facilitating cell cycle progression.These findings offer potential avenues for enhancing cloning efficiency,with implications for evolutionary biology and the conservation of valuable germplasm resources.展开更多
Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in man...Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes ...Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method,and modified with polyethylene glycol-polylactic-co-glycolic acid(PEG-PLGA)to form nanocarriers(PTX-Exo-NPs).The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer;drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography;drug release behavior was evaluated in vitro under simulated acidic(pH 5.5)and physiological(pH 7.4)conditions;MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation,apoptosis,and cell cycle distribution of HEC-1A cells.Results:PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of(128.5±5.2)nm,PTX encapsulation efficiency of 92.3%±2.1%,and drug loading capacity of 15.6%±0.8%.Drug release rate in the acidic environment(85.3%±2.1%within 72 h)was significantly higher than that in the physiological environment(48.0%±1.7%).In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX,with a lower IC50(0.64μM vs 4.70μM),and could induce cell apoptosis(apoptosis rate:28.7%±2.1%vs 14.2%±1.5%)and promote cell cycle arrest(G_2/M rate:45.3%±3.2%).Conclusion:PTX-Exo-NPs exhibit pH-responsive characteristics,which can target drug release through the acidic microenvironment,enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells,thus serving as a potential strategy for targeted therapy of endometrial tumors.展开更多
Background:Diabetes mellitus(DM),a metabolic disorder that leads to chronic hyperglycemia,is one of the topmost global public health concerns according to the International Diabetes Federation.Adropin is a peptide hor...Background:Diabetes mellitus(DM),a metabolic disorder that leads to chronic hyperglycemia,is one of the topmost global public health concerns according to the International Diabetes Federation.Adropin is a peptide hormone that is primarily involved in energy homeostasis,but its involvement in other biological activities such as lowering hyperlipidemia,and diminishing insulin resistance has also been reported.In this study,we aimed to explore additional effects of adropin on oxidative stress,inflammation,and cell proliferation in an animal model of type 1 DM.Methods:To achieve our aim,normal and diabetic Wistar rats were treated with adropin(2.1μg/kg/day)for a period of 10 days.Pancreatic tissue samples were collected for histomorphological analysis and inflammation assay,while blood was collected for oxidative stress assay.Results:Our results showed that diabetes induction stimulated cell proliferation in both exocrine and endocrine pancreas,and adropin dramatically attenuated this effect in pancreatic exocrine tissue,but not in the islet of Langerhans.In addition,adropin significantly increased glutathione reductase expression in pancreatic tissue,and augmented serum total glutathione in the diabetic rats compared to diabetic untreated rats.Conclusion:Our study indicates the potential role of adropin in alleviating oxidative stress in DM.展开更多
In this paper,we focus on compelling evidence showing that MEX3A is significantly overexpressed in hepatocellular carcinoma(HCC)and correlates with poor prognosis.A recent study by Ji et al highlights MEX3A’s role in...In this paper,we focus on compelling evidence showing that MEX3A is significantly overexpressed in hepatocellular carcinoma(HCC)and correlates with poor prognosis.A recent study by Ji et al highlights MEX3A’s role in driving proliferation and migration via the RORA/β-catenin axis and epithelial-mesenchymal transition,positioning it as a potential biomarker and therapeutic target.This study addresses a critical gap in understanding HCC pathogenesis and offers valuable mechanistic insights.展开更多
The published article titled“MicroRNA-133b Inhibits Cell Proliferation and Invasion in Osteosarcoma by Targeting Sirt1”has been retracted from Oncology Research,Vol.25,No.9,2017,pp.1421–1430.
The published article titled“Overexpression of miR-1283 Inhibits Cell Proliferation and Invasion of Glioma Cells by Targeting ATF4”has been retracted from Oncology Research,Vol.27,No.3,2019,pp.325–334.
The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research...The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.展开更多
The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp...The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp.39–45.展开更多
文摘The published article titled“MicroRNA-133b Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.
基金supported by NIH grants,Nos.R01NS125074,R01AG083164,R01NS107365,and R21NS127177(to YL),1F31NS129204-01A1(to KW)and Albert Ryan Fellowship(to KW).
文摘Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo.
基金funded by the Sichuan Science and Technology Program(2021ZDZX0009)the earmarked fund from the National Natural Science Foundation of China(31972577)。
文摘Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates dextran sulfate sodium(DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions.However,the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear.This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.Methods A total of 6021-day-old weaned female piglets were randomly assigned into three groups based on weight:the control group(basal diet with physiological saline gavage),the DSS group(basal diet with 5%DSS gavage),and the DSS+LA group(2%lactate diet with 5%DSS gavage).There were 10 replicates per treatment,with 2 piglets per replicate.Jejunal morphology was assessed via hematoxylin and eosin staining,while Western blotting quantified the protein levels of proliferation markers,including cluster of differentiation 24(CD24),cyclin D1,and wingless/integrated(Wnt)/β-catenin signaling components.In vitro,0.08%DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2(IPEC-J2)cells(n=4)were assessed for viability(Cell Counting Kit-8 assay),apoptosis(flow cytometry),and proliferation parameters,including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5+)stem cell quantification.Results In vivo,DSS administration induced jejunal villus shortening(P<0.05),downregulated protein levels of CD24,cyclin D1,casein kinase 1(CK1),and dishevelled-2(DVL2)(P<0.05).In vitro,DSS promoted apoptosis,inhibited proliferation,diminished the Lgr5+cell populations(P<0.05),and reduced S-phase cell proportions(P<0.05).Conversely,lactate supplementation ameliorated DSS-induced villus atrophy(P<0.05),restored CD24,cyclin D1,CK1,and DVL2 protein levels(P<0.05).Furthermore,in vitro,sodium lactate attenuated DSS-induced apoptosis(P<0.05),enhanced IPEC-J2 proliferation(P<0.05),expanded Lgr5+cells(P<0.05),and increased S-phase progression(P<0.05).Conclusions In summary,lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis.This study provides novel mechanistic evidence supporting lactate's therapeutic potential for IBD management.
文摘Oncology Research Editorial Office Published:23 March 2026 The published article titled“MicroRNA 125a-5p Inhibits Cell Proliferation and Induces Apoptosis in Hepatitis B Virus-Related Hepatocellular Carcinoma by Downregulation of ErbB3”has been retracted from Oncology Research,Vol.27,No.4,2019,pp.449-458.DOI:10.3727/096504017X15016337254623 URL:https://www.techscience.com/or/v27n4/48558.
文摘Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.
基金supported by the National Natural Science Foundation of China(32360837 and 32341052)the STI2030 Major Projects,China(2023ZW0404803)+8 种基金the Inner Mongolia Open Competition Projects,China(2022JBGS0025)the Inner Mongolia Science and Technology Leading Team,China(2022LJRC0006)the Inner Mongolia Science and Technology Major Projects,China(2021ZD0009,2021ZD0008,2022ZD0008,2023KJHZ0028)the Inner Mongolia Young Talents Projects,China(NJYT23138)the Inner Mongolia Natural Science Foundation,China(2023MS03004)the Central Government Guides Development,China(2022ZY0212)the National Agricultural Science and Technology Project of China(NK2022130203)the Collaborative Innovation among Universities in Hohhot,China(XTCX2023-06)the Ministry of Education Engineering Centre Project,China(JYBGCSYS2022)。
文摘Myostatin(MSTN)is principally expressed in skeletal muscle and negatively regulates muscle growth and development.MSTN mutation can induce muscle overgrowth in cattle by activating cell proliferation,presenting a“double-muscle”phenotype.However,the specific regulatory mechanism is still unclear.Here,we found that Ca^(2+)content in muscle tissue and muscle satellite cells of MSTN mutated(MSTN^(–/–))cattle were significantly increased compared to wild-type(WT).Furthermore,transcriptome analysis of muscle satellite cells revealed that TRPC4 was significantly increased in MSTN^(–/–)cattle.And the expression of TRPC4 in muscle tissue of MSTN^(–/–)cattle was detected by RT-qPCR and Western blot,which was significantly higher than that of WT.These results suggested that MSTN mutation promoted muscle satellite cells proliferation through activation of TRPC4 channel.To further verify,ML204,a specific inhibitor of TRPC4,was used to treat MSTN^(–/–)muscle satellite cells.We found that cell proliferation was inhibited,calcineurin expression was downregulated,and the entry of NFATc3 into nuclei was reduced,which was similar to WT group.Thus,MSTN mutation leads to the activation of TRPC4 channel,which increases intracellular Ca^(2+)content,further activates calcineurin/NFATc3 pathway,and ultimately promotes the proliferation of muscle satellite cells.
文摘Objectives:Tumor recurrence is a major determinant of poor prognosis in hepatocellular carcinoma(HCC),yet its cellular and molecular basis remains incompletely understood.This study aimed to identify recurrenceassociated genes at single-cell resolution and to develop a prognostic model for predicting survival outcomes and immunotherapy responsiveness in HCC.Methods:Single-cell RNA sequencing data from 12 primary and 6 recurrent HCC samples were integrated and analyzed to identify genes characteristic of recurrence.After quality control,principal component analysis,and t-SNE-based clustering were used to identify highly variable genes for cell clustering and annotation.Based on macrophage characteristic genes,a recurrence-related risk score was constructed using a LASSOCox regression model,and a nomogram integrating clinical variables was developed.Prognostic performance was assessed using Kaplan-Meier analysis and time-dependent ROC curves.Immune infiltration profiling was performed to compare immune characteristics between risk groups defined by the prognostic model.Multivariate Cox regression was applied to identify independent prognostic biomarkers,which were subsequently validated by cell function experiments.Results:The risk model effectively stratified patients into high-and low-risk groups with distinct survival outcomes,demonstrating high predictive accuracy for 1-,3-,and 5-year survival.High-risk patients showed altered immune profiles and a reduced predicted response to immunotherapy.GRID2,RNF186,and SLC4A10 were identified as independent prognostic genes,with RNF186 promoting HCC cell proliferation in a SESN2-dependent manner.Conclusion:This prognostic model provides new insights into precision medicine and immunotherapy for HCC,highlighting the potential clinical significance of RNF186 as a therapeutic target.
基金supported by the National Natural Science Foundation of China(82260716)the Key Research and Development Program of Ningxia(2023BEG02010).
文摘Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study aims to identify a novel small molecule,synthesized via proteolysis-targeting chimeras(PROTACs),capable of degrading BCL6,thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.Methods:The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas(TCGA)database and the Human Protein Atlas.Western blotting assays confirmed BCL6 expression in tumor cell lines,leading to the identification of the small molecule compound DZ-865B.To evaluate DZ-865B’s in vitro efficacy,multiple assays were performed,including protein immunoblotting,immunofluorescence,reverse transcription quantitative PCR,EDU proliferation,and soft agar cloning assays.Results:TCGA analysis revealed significant overexpression of BCL6 in DLBCL(p<0.05),corroborated by immunohistological staining and western blotting.DZ-865B induced BCL6 degradation in DLBCL cell lines(OCI-LY-1 and SU-DHL-4)in a concentration-and time-dependent manner,and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway.Notably,DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression,leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis,effectively suppressing DLBCL cell growth.Conclusion:This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells,promoting apoptosis and inhibiting cellular proliferation.These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.
基金supported by the National Natural Science Foundation of China,No.81571211(to FL)the Natural Science Foundation of Shanghai,No.22ZR1476800(to CH)。
文摘Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.
文摘Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.
基金National Natural Science Foundation of China(Grant No.31600549).
文摘To explore the potential utilization of Elaeagnus mollis,we conducted a comprehensive assessment of its phytochemical composition,antioxidant properties,cholinesterase inhibition,and anti-HepG2 cell proliferation activity across different plant parts(branch wood,branch bark,and pericarp)using various solvents(water,methanol,ethanol,and n-hexane).Our findings revealed that water extracts displayed superior antioxidant activities in ABTS and RP assays,while methanol extracts exhibited better performance in DPPH and FRAP assays.Moreover,methanol extracts demonstrated the highest effectiveness against anti-HepG2 cell proliferation,whereas n-hexane extracts showed greater efficiency in cholinesterase inhibition.Notably,branch bark extracts exhibited the highest levels of phytochemical compounds,with both branch bark and pericarp extracts demonstrating significant effects in cholinesterase inhibition and anti-HepG2 cell proliferation.Correlation analysis indicated that phytochemical compounds were primarily responsible for the observed biological activities.Overall,extracts from the branch bark and pericarp of E.mollis showed promising potential for antioxidant and anticancer activities,suggesting their suitability for applications in the pharmaceutical industry as health-promoting products.
基金supported by the National Natural Science Foundation of China (32060755)Natural Science Foundation of Inner Mongolia (2024MS03001)+7 种基金Inner Mongolia Autonomous Region Open Competition Projects (2022JBGS0018)Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region (NJYT23090)Inner Mongolia Autonomous Region Science and Technology Leading Team (2022LJRC0006)Inner Mongolia Autonomous Region Science and Technology Major Project (2021ZD0009)Major Agricultural Science and Technology Project of the Ministry of Agriculture and Rural Affairs (NK2022130203)Central Government Guides Local Science and Technology Development Funds (2022ZY0212)Inner Mongolia Autonomous Region High-level Talent Support ProgramInner Mongolia University Chief Scientist Program。
文摘Somatic cell nuclear transfer(SCNT)has been successfully employed across various mammalian species,yet cloned animals consistently exhibit low pregnancy rates,primarily due to placental abnormalities such as hyperplasia and hypertrophy.This study investigated the involvement of the Hippo signaling pathway in aberrant placentaldevelopmentinSCNT-inducedbovine pregnancies.SCNT-derived cattle exhibited placental hypertrophy,including enlarged abdominal circumference and altered placental cotyledon morphology.RNA sequencing analysis indicated significant dysregulation of Hippo signaling pathway genes in SCNT placentas.Coexpression of YAP1 and CCND1 was observed in cloned blastocysts,placental tissues,and bovine placental mesenchymal stem cells(bPMSCs).Manipulation of YAP1expression demonstrated the capacity to regulate bPMSC proliferation.Experimental assays confirmed the direct binding of YAP1 to CCND1,which subsequently promoted CCND1 expression in bPMSCs.Furthermore,inhibition of CDK6,a downstream target of CCND1,attenuated SCNT bPMSC proliferation.This study identified YAP1 as a key regulatory component within the Hippo signaling pathway that drives placental hyperplasia in cloned cattle through up-regulation of CCND1-CDK6 expression,facilitating cell cycle progression.These findings offer potential avenues for enhancing cloning efficiency,with implications for evolutionary biology and the conservation of valuable germplasm resources.
文摘Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
文摘Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method,and modified with polyethylene glycol-polylactic-co-glycolic acid(PEG-PLGA)to form nanocarriers(PTX-Exo-NPs).The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer;drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography;drug release behavior was evaluated in vitro under simulated acidic(pH 5.5)and physiological(pH 7.4)conditions;MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation,apoptosis,and cell cycle distribution of HEC-1A cells.Results:PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of(128.5±5.2)nm,PTX encapsulation efficiency of 92.3%±2.1%,and drug loading capacity of 15.6%±0.8%.Drug release rate in the acidic environment(85.3%±2.1%within 72 h)was significantly higher than that in the physiological environment(48.0%±1.7%).In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX,with a lower IC50(0.64μM vs 4.70μM),and could induce cell apoptosis(apoptosis rate:28.7%±2.1%vs 14.2%±1.5%)and promote cell cycle arrest(G_2/M rate:45.3%±3.2%).Conclusion:PTX-Exo-NPs exhibit pH-responsive characteristics,which can target drug release through the acidic microenvironment,enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells,thus serving as a potential strategy for targeted therapy of endometrial tumors.
基金supported by research grants from the United Arab Emirates University[Grant#:G00003388,G00002809,G00003627,31M374].
文摘Background:Diabetes mellitus(DM),a metabolic disorder that leads to chronic hyperglycemia,is one of the topmost global public health concerns according to the International Diabetes Federation.Adropin is a peptide hormone that is primarily involved in energy homeostasis,but its involvement in other biological activities such as lowering hyperlipidemia,and diminishing insulin resistance has also been reported.In this study,we aimed to explore additional effects of adropin on oxidative stress,inflammation,and cell proliferation in an animal model of type 1 DM.Methods:To achieve our aim,normal and diabetic Wistar rats were treated with adropin(2.1μg/kg/day)for a period of 10 days.Pancreatic tissue samples were collected for histomorphological analysis and inflammation assay,while blood was collected for oxidative stress assay.Results:Our results showed that diabetes induction stimulated cell proliferation in both exocrine and endocrine pancreas,and adropin dramatically attenuated this effect in pancreatic exocrine tissue,but not in the islet of Langerhans.In addition,adropin significantly increased glutathione reductase expression in pancreatic tissue,and augmented serum total glutathione in the diabetic rats compared to diabetic untreated rats.Conclusion:Our study indicates the potential role of adropin in alleviating oxidative stress in DM.
基金Supported by Youth Foundation of Henan Scientific Committee,No.202300410416Henan Province Medical Science,Technology Breakthrough Plan Project,No.LHGJ20190033.
文摘In this paper,we focus on compelling evidence showing that MEX3A is significantly overexpressed in hepatocellular carcinoma(HCC)and correlates with poor prognosis.A recent study by Ji et al highlights MEX3A’s role in driving proliferation and migration via the RORA/β-catenin axis and epithelial-mesenchymal transition,positioning it as a potential biomarker and therapeutic target.This study addresses a critical gap in understanding HCC pathogenesis and offers valuable mechanistic insights.
文摘The published article titled“MicroRNA-133b Inhibits Cell Proliferation and Invasion in Osteosarcoma by Targeting Sirt1”has been retracted from Oncology Research,Vol.25,No.9,2017,pp.1421–1430.
文摘The published article titled“Overexpression of miR-1283 Inhibits Cell Proliferation and Invasion of Glioma Cells by Targeting ATF4”has been retracted from Oncology Research,Vol.27,No.3,2019,pp.325–334.
文摘The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.
文摘The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp.39–45.
