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
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Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.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
Objectives Therapeutic strategies for enhancing bone regeneration and combating osteoporosis remain a significant unmet medical need.This study aims to elucidate Lithospermic acid(LA)’s regulatory effects on osteobla...Objectives Therapeutic strategies for enhancing bone regeneration and combating osteoporosis remain a significant unmet medical need.This study aims to elucidate Lithospermic acid(LA)’s regulatory effects on osteoblast proliferation and differentiation,investigating its viability as a bone-healing agent.Methods This study employed various cellular and molecular biology experiments to assess the effects of LA on the viability,proliferation,cell cycle,apoptosis,differentiation,mineralization,and migration of MC3T3-E1 osteoblasts.Immunofluorescence and Western blot analyses were conducted to detect the expression of proteins related to the Wnt/β-catenin signaling pathway,investigating the regulatory mechanisms by which LA promotes osteoblast proliferation and differentiation.Additionally,Wnt inhibitor dickkopf-1(DKK-1)andβ-catenin-silenced cell models were used to further validate the role of LA in modulating this signaling pathway.Results LA significantly promoted osteoblast proliferation without apparent cytotoxicity.Flow cytometry showed that LA regulated the cell cycle by reducing G0/G1 phase arrest and promoting G2/M phase progression.Western blot results indicated that LA upregulated the expression of proteins associated with cell proliferation and enhanced osteoblast differentiation and mineralization.Immunofluorescence and Western blot analyses further confirmed that LA markedly increased the expression of Wnt andβ-catenin,facilitatingβ-catenin nuclear translocation.Treatment with the DKK-1 inhibitor significantly diminished the proliferative and differentiation-promoting effects of LA,confirming the critical role of this pathway.β-catenin knockdown experiments further substantiated its central role in LA-mediated regulation.Conclusion This study confirms that LA promotes osteoblast proliferation,differentiation,mineralization,and migration by activating the Wnt/β-catenin signaling pathway.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
BACKGROUND Over the years,the numbers of treatment options for colorectal cancer(CRC)have increased,leading to notable improvements in the overall survival of CRC patients.Although therapy may initially yield positive...BACKGROUND Over the years,the numbers of treatment options for colorectal cancer(CRC)have increased,leading to notable improvements in the overall survival of CRC patients.Although therapy may initially yield positive results,the development of drug resistance can result in treatment failure and cancer recurrence.This resistance is often attributed to the presence of cancer stem cells(CSCs).These CSCs not only contribute to therapeutic resistance but also play crucial roles in the initiation and development of tumor metastasis.AIM To investigate the antitumor effects of SH-4-54,which are mediated by targeting CSCs relative to treatment outcomes.METHODS CSCs were enriched by culturing CRC cells in serum-free medium.Hallmarks of stemness and IL-6/JAK2/STAT3 signaling were detected by Western blotting.Indicators of CSC malignancy,including proliferation,invasion,and tumor formation,were measured.RESULTS In this study,we employed SH-4-54,which exhibits anticancer activity in solid tumors through targeting the SH2 domain of both the signal transducer and activator of transcription(STAT)3 and the STAT5,and evaluated its effects on stemness and chemoresistance in colorectal CSCs.As expected,SH-4-54 treatment inhibited the phosphorylation of STAT3(p-STAT3)and decreased the percentage of ALDH1A1-positive CRC cells.The addition of SH-4-54 dissociated colorectal spheroids and decreased the expression of stemness markers,including ALDH1A1,CD44 and Nanog.SH-4-54 treatment decreased IL-6/JAK2/STAT3 signaling by inhibiting p-STAT3 and thus inhibited spheroid formation by SW480 and LoVo cells.Moreover,SH-4-54 treatment inhibited indicators of malignancy,including cell proliferation,invasion,and tumor formation,in CSCs in vitro and in vivo.Notably,SH-4-54 treatment significantly increased chemosensitivity to oxaplatin.CONCLUSION Taken together,these results indicate that SH-4-54 is a promising molecule that exerts antitumor effects on colorectal CSCs by inhibiting STAT3 signaling.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
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
Objectives:Novel drug delivery systems have been designed to enhance local drug concentrations while reducing side effects conducive to improved breast cancer treatment outcomes.This study aimed to identify the anti-c...Objectives:Novel drug delivery systems have been designed to enhance local drug concentrations while reducing side effects conducive to improved breast cancer treatment outcomes.This study aimed to identify the anti-cancer function of zeolite imidazole ester-based material loaded with camptothecin nanoparticles.Methods:We utilized a zeolitic imidazolate backbone material to fabricate 9-hydroxycamptothecin nanoparticles and investigated their impact on breast cancer cell proliferation.Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed changes in the carrier skeleton of the loaded 9-hydroxyl camptothecin,characterized by a reduction in surface smoothness,accompanied by slight collapses and folds on the particle surface.Notably,we detected vibration of the benzene ring in the 9-hydroxycamptothecin structure within the nanoparticles.Cell proliferation was tested by CCK-8.Protein expression was measured byWestern blot.The efficacy of nanoparticles was evaluated by animal experiments.Results:In this study,we utilized a zeolitic imidazolate backbone material to fabricate 9-hydroxycamptothecin(9-HCPT)nanoparticles and investigated their impact on breast cancer cell proliferation.Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed changes in the carrier skeleton of the loaded 9-hydroxyl camptothecin,characterized by a reduction in surface smoothness,accompanied by slight collapses and folds on the particle surface.Notably,we detected vibration of the benzene ring in the 9-HCPT structure within the nanoparticles.Using the CCK-8 method,we evaluated the inhibitory effect of these nanoparticles on breast cancer cells and observed a significant reduction in the cytotoxicity of camptothecin(CPT)when incorporated into the zeolite imidazole ester skeleton material.Immunoblot analysis showed upregulation of cyclic GMP-AMP synthase(cGAS),stimulator of interferon genes(STING),andNF-κB-p65 in response to the nanoparticles.These results showed that our nanoparticles might be a useful drug delivery strategy to overcome breast cancer drug resistance.Conclusion:Thefindings of this study suggest that nanoparticles loaded with CPT and formed fromzeolite imidazole ester backbone material possess immune-enhancing properties that could suppress breast cancer progression.Accordingly,these nanoparticles hold promise as potential lead compounds for combined immunotherapy in breast cancer treatment.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.
BACKGROUND Ras-related protein Rab24,which belongs to the small GTPase family,plays a crucial role in regulating intracellular protein trafficking.Dysregulation of Rab24 has been recently identified in hepatocellular ...BACKGROUND Ras-related protein Rab24,which belongs to the small GTPase family,plays a crucial role in regulating intracellular protein trafficking.Dysregulation of Rab24 has been recently identified in hepatocellular carcinoma(HCC).However,its clinical significance and tumor related effects remain to be further clarified.AIM To explore the expression pattern of Rab24 and its role in HCC progression.METHODS The expression profile of Rab24 was tested in HCC tissues together with adjacent tissues from transcriptional,mRNA,and protein levels.The prognostic role of Rab24 in HCC was assessed by univariate and multivariate analyses.Clinical outcomes were evaluated by the Kaplan-Meier analysis and log-rank test.The effect of Rab24 on cell proliferation was tested through cellular experiments and xenograft experiments.RESULTS Rab24 expression was elevated in HCC tissues compared to adjacent liver tissues.High expression of Rab24 was significantly associated with larger tumor size and advanced tumor stage.Moreover,HCC patients with high Rab24 expression showed poorer overall survival,and Rab24 was identified as an independent prognosis factor according to multivariate analysis.By using overexpression and shRNA knockdown strategies in HCC cell lines,we found that Rab24 can promote HCC proliferation.Finally,we validated that silencing Rab24 significantly attenuated xenograft growth in vivo.CONCLUSION Our study demonstrated that high expression of Rab24 was significantly correlated with poorer prognosis of HCC patients,indicating the potential of Rab24 as a novel clinical biomarker and therapeutic target.展开更多
The published article titled“Triptolide inhibits proliferation and migration of human neuroblastoma SH-SY5Y cells by upregulating microRNA-181a”has been retracted from Oncology Research,Vol.26,No.8,2018,PP.1235-1243.
The published article titled“MicroRNA-33b Inhibits the Proliferation andMigration of Osteosarcoma Cells via TargetingHypoxia-Inducible Factor-1α”has been retracted from Oncology Research,Vol.25,No.3,2017,pp.397–405.
Objectives:Keratin 6A(KRT6A)has been implicated in the progression of multiple malignancies;however,its expression pattern and biological role in cervical cancer(CC)have not been elucidated.This study aims to investig...Objectives:Keratin 6A(KRT6A)has been implicated in the progression of multiple malignancies;however,its expression pattern and biological role in cervical cancer(CC)have not been elucidated.This study aims to investigate KRT6A expression in CC tissues and evaluate its effects on cellular proliferation,migration,and invasion,thereby assessing its potential as a biomarker and therapeutic target.Methods:Differentially expressed genes were screened from the Gene Expression Omnibus(GEO)dataset(GSE9750)using the thresholds∣log2FC∣>2 and false discovery rate(FDR)<0.05.Immunohistochemistry was performed to evaluate KRT6A protein expression in tumor tissues.Stable KRT6A knockdown was established in CC cell lines to assess proliferation,colony formation,migration,and invasion in vitro.A nude-mouse xenograft model was used to evaluate tumor growth in vivo.Results:KRT6A expression was significantly increased in CC tissues relative to adjacent non-tumor tissues(p=0.019).Patients with KRT6A-positive tumors had a significantly lower 3-year progression-free survival(PFS)rate than those with KRT6Anegative tumors(45.16%vs.78.57%;p=0.009).KRT6A was identified as an independent prognostic indicator for CC(p=0.044).In vitro,KRT6A silencing significantly reduced colony formation,proliferation,migration,and invasion in SiHa and HeLa cells in comparison to controls(p<0.05).In vivo,tumors in the KRT6A knockdown group were significantly smaller,with reduced expression of both KRT6A and Ki-67 in tumor tissues(p<0.05).Conclusion:KRT6A is overexpressed in CC and associates with adverse clinicopathological features and poor PFS.Knockdown of KRT6A suppresses cell proliferation,migration,and invasion,indicating that KRT6A may represent a promising prognostic biomarker and potential target for treating CC.展开更多
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.
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.
基金funded by Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(2023ZL128)Zhejiang Province Medical and Health Science and Technology Project(2022504276)Hangzhou Municipal Health and Family Planning Science and Technology Program General Project(A20210086).
文摘Objectives Therapeutic strategies for enhancing bone regeneration and combating osteoporosis remain a significant unmet medical need.This study aims to elucidate Lithospermic acid(LA)’s regulatory effects on osteoblast proliferation and differentiation,investigating its viability as a bone-healing agent.Methods This study employed various cellular and molecular biology experiments to assess the effects of LA on the viability,proliferation,cell cycle,apoptosis,differentiation,mineralization,and migration of MC3T3-E1 osteoblasts.Immunofluorescence and Western blot analyses were conducted to detect the expression of proteins related to the Wnt/β-catenin signaling pathway,investigating the regulatory mechanisms by which LA promotes osteoblast proliferation and differentiation.Additionally,Wnt inhibitor dickkopf-1(DKK-1)andβ-catenin-silenced cell models were used to further validate the role of LA in modulating this signaling pathway.Results LA significantly promoted osteoblast proliferation without apparent cytotoxicity.Flow cytometry showed that LA regulated the cell cycle by reducing G0/G1 phase arrest and promoting G2/M phase progression.Western blot results indicated that LA upregulated the expression of proteins associated with cell proliferation and enhanced osteoblast differentiation and mineralization.Immunofluorescence and Western blot analyses further confirmed that LA markedly increased the expression of Wnt andβ-catenin,facilitatingβ-catenin nuclear translocation.Treatment with the DKK-1 inhibitor significantly diminished the proliferative and differentiation-promoting effects of LA,confirming the critical role of this pathway.β-catenin knockdown experiments further substantiated its central role in LA-mediated regulation.Conclusion This study confirms that LA promotes osteoblast proliferation,differentiation,mineralization,and migration by activating the Wnt/β-catenin signaling pathway.
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.
文摘BACKGROUND Over the years,the numbers of treatment options for colorectal cancer(CRC)have increased,leading to notable improvements in the overall survival of CRC patients.Although therapy may initially yield positive results,the development of drug resistance can result in treatment failure and cancer recurrence.This resistance is often attributed to the presence of cancer stem cells(CSCs).These CSCs not only contribute to therapeutic resistance but also play crucial roles in the initiation and development of tumor metastasis.AIM To investigate the antitumor effects of SH-4-54,which are mediated by targeting CSCs relative to treatment outcomes.METHODS CSCs were enriched by culturing CRC cells in serum-free medium.Hallmarks of stemness and IL-6/JAK2/STAT3 signaling were detected by Western blotting.Indicators of CSC malignancy,including proliferation,invasion,and tumor formation,were measured.RESULTS In this study,we employed SH-4-54,which exhibits anticancer activity in solid tumors through targeting the SH2 domain of both the signal transducer and activator of transcription(STAT)3 and the STAT5,and evaluated its effects on stemness and chemoresistance in colorectal CSCs.As expected,SH-4-54 treatment inhibited the phosphorylation of STAT3(p-STAT3)and decreased the percentage of ALDH1A1-positive CRC cells.The addition of SH-4-54 dissociated colorectal spheroids and decreased the expression of stemness markers,including ALDH1A1,CD44 and Nanog.SH-4-54 treatment decreased IL-6/JAK2/STAT3 signaling by inhibiting p-STAT3 and thus inhibited spheroid formation by SW480 and LoVo cells.Moreover,SH-4-54 treatment inhibited indicators of malignancy,including cell proliferation,invasion,and tumor formation,in CSCs in vitro and in vivo.Notably,SH-4-54 treatment significantly increased chemosensitivity to oxaplatin.CONCLUSION Taken together,these results indicate that SH-4-54 is a promising molecule that exerts antitumor effects on colorectal CSCs by inhibiting STAT3 signaling.
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 grants from the Guangdong Basic and Applied Basic Research Foundation(No.2023B1515130009)the Science and Technology Bureau of Foshan(No.FS0AA-KJ819-4901-0082).
文摘Objectives:Novel drug delivery systems have been designed to enhance local drug concentrations while reducing side effects conducive to improved breast cancer treatment outcomes.This study aimed to identify the anti-cancer function of zeolite imidazole ester-based material loaded with camptothecin nanoparticles.Methods:We utilized a zeolitic imidazolate backbone material to fabricate 9-hydroxycamptothecin nanoparticles and investigated their impact on breast cancer cell proliferation.Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed changes in the carrier skeleton of the loaded 9-hydroxyl camptothecin,characterized by a reduction in surface smoothness,accompanied by slight collapses and folds on the particle surface.Notably,we detected vibration of the benzene ring in the 9-hydroxycamptothecin structure within the nanoparticles.Cell proliferation was tested by CCK-8.Protein expression was measured byWestern blot.The efficacy of nanoparticles was evaluated by animal experiments.Results:In this study,we utilized a zeolitic imidazolate backbone material to fabricate 9-hydroxycamptothecin(9-HCPT)nanoparticles and investigated their impact on breast cancer cell proliferation.Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed changes in the carrier skeleton of the loaded 9-hydroxyl camptothecin,characterized by a reduction in surface smoothness,accompanied by slight collapses and folds on the particle surface.Notably,we detected vibration of the benzene ring in the 9-HCPT structure within the nanoparticles.Using the CCK-8 method,we evaluated the inhibitory effect of these nanoparticles on breast cancer cells and observed a significant reduction in the cytotoxicity of camptothecin(CPT)when incorporated into the zeolite imidazole ester skeleton material.Immunoblot analysis showed upregulation of cyclic GMP-AMP synthase(cGAS),stimulator of interferon genes(STING),andNF-κB-p65 in response to the nanoparticles.These results showed that our nanoparticles might be a useful drug delivery strategy to overcome breast cancer drug resistance.Conclusion:Thefindings of this study suggest that nanoparticles loaded with CPT and formed fromzeolite imidazole ester backbone material possess immune-enhancing properties that could suppress breast cancer progression.Accordingly,these nanoparticles hold promise as potential lead compounds for combined immunotherapy in breast cancer treatment.
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BACKGROUND Ras-related protein Rab24,which belongs to the small GTPase family,plays a crucial role in regulating intracellular protein trafficking.Dysregulation of Rab24 has been recently identified in hepatocellular carcinoma(HCC).However,its clinical significance and tumor related effects remain to be further clarified.AIM To explore the expression pattern of Rab24 and its role in HCC progression.METHODS The expression profile of Rab24 was tested in HCC tissues together with adjacent tissues from transcriptional,mRNA,and protein levels.The prognostic role of Rab24 in HCC was assessed by univariate and multivariate analyses.Clinical outcomes were evaluated by the Kaplan-Meier analysis and log-rank test.The effect of Rab24 on cell proliferation was tested through cellular experiments and xenograft experiments.RESULTS Rab24 expression was elevated in HCC tissues compared to adjacent liver tissues.High expression of Rab24 was significantly associated with larger tumor size and advanced tumor stage.Moreover,HCC patients with high Rab24 expression showed poorer overall survival,and Rab24 was identified as an independent prognosis factor according to multivariate analysis.By using overexpression and shRNA knockdown strategies in HCC cell lines,we found that Rab24 can promote HCC proliferation.Finally,we validated that silencing Rab24 significantly attenuated xenograft growth in vivo.CONCLUSION Our study demonstrated that high expression of Rab24 was significantly correlated with poorer prognosis of HCC patients,indicating the potential of Rab24 as a novel clinical biomarker and therapeutic target.
文摘The published article titled“Triptolide inhibits proliferation and migration of human neuroblastoma SH-SY5Y cells by upregulating microRNA-181a”has been retracted from Oncology Research,Vol.26,No.8,2018,PP.1235-1243.
文摘The published article titled“MicroRNA-33b Inhibits the Proliferation andMigration of Osteosarcoma Cells via TargetingHypoxia-Inducible Factor-1α”has been retracted from Oncology Research,Vol.25,No.3,2017,pp.397–405.
基金supported by Yixing Taodu Light Science and Technology Research Plan,Grant Number:2024SF14.
文摘Objectives:Keratin 6A(KRT6A)has been implicated in the progression of multiple malignancies;however,its expression pattern and biological role in cervical cancer(CC)have not been elucidated.This study aims to investigate KRT6A expression in CC tissues and evaluate its effects on cellular proliferation,migration,and invasion,thereby assessing its potential as a biomarker and therapeutic target.Methods:Differentially expressed genes were screened from the Gene Expression Omnibus(GEO)dataset(GSE9750)using the thresholds∣log2FC∣>2 and false discovery rate(FDR)<0.05.Immunohistochemistry was performed to evaluate KRT6A protein expression in tumor tissues.Stable KRT6A knockdown was established in CC cell lines to assess proliferation,colony formation,migration,and invasion in vitro.A nude-mouse xenograft model was used to evaluate tumor growth in vivo.Results:KRT6A expression was significantly increased in CC tissues relative to adjacent non-tumor tissues(p=0.019).Patients with KRT6A-positive tumors had a significantly lower 3-year progression-free survival(PFS)rate than those with KRT6Anegative tumors(45.16%vs.78.57%;p=0.009).KRT6A was identified as an independent prognostic indicator for CC(p=0.044).In vitro,KRT6A silencing significantly reduced colony formation,proliferation,migration,and invasion in SiHa and HeLa cells in comparison to controls(p<0.05).In vivo,tumors in the KRT6A knockdown group were significantly smaller,with reduced expression of both KRT6A and Ki-67 in tumor tissues(p<0.05).Conclusion:KRT6A is overexpressed in CC and associates with adverse clinicopathological features and poor PFS.Knockdown of KRT6A suppresses cell proliferation,migration,and invasion,indicating that KRT6A may represent a promising prognostic biomarker and potential target for treating CC.
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.
