Objective:Actin filament-associated protein 1 like 1(AFAP1L1)is an adaptor protein lacking enzymatic and transcriptional activity,but the AFAP1L1 gene functions as an oncogene in colorectal cancer and gastric cancers....Objective:Actin filament-associated protein 1 like 1(AFAP1L1)is an adaptor protein lacking enzymatic and transcriptional activity,but the AFAP1L1 gene functions as an oncogene in colorectal cancer and gastric cancers.This study aims to investigate the role of AFAP1L1 in glioma and to explore changes in AFAP1L1 expression during glioma progression.Methods:Clinical and transcriptomic data of glioma patients were downloaded from The Cancer Genome Atlas(TCGA),the Chinese Glioma Genome Atlas(CGGA),and the Gene Expression Omnibus(GEO)databases to analyze the associations between AFAP1L1 expression and glioma prognosis,somatic mutations,immune cell infiltration,and enriched signaling pathways.Western blotting and real-time polymerase chain reaction(PCR)were used to detect AFAP1L1 messenger RNA(mRNA)and protein expression in glioma patients.Results:Patients with high AFAP1L1 expression had poorer prognosis,and AFAP1L1 was identified as an independent risk factor for glioma.In addition,glioma patients with high AFAP1L1 expression exhibited lower levels of somatic mutations,including amplification of oncogenes such as epidermal growth factor receptor and deletion of tumor suppressor genes such as cyclin-dependent kinase inhibitor 2A(CDKN2A).Estimation of STromal and Immune cells in Malignant Tumours using Expression(ESTIMATE)algorithm analysis showed that AFAP1L1 expression was positively correlated with the immune microenvironment.Tumor immune dysfunction and exclusion(TIDE)analysis indicated that glioma patients with high AFAP1L1 expression responded poorly to immunotherapy.Single cell analysis showed that AFAP1L1 expression was mainly concentrated in glioma cells.Enrichment analysis suggested that AFAP1L1 was potentially associated with small guanosine triphosphatases(GTPases),hypoxia-inducible factor-1(HIF-1),focal adhesion,and mitogen-activated protein kinase(MAPK)signaling pathways.Conclusion:AFAP1L1 is a novel biomarker indicating glioma progression and a potential therapeutic target for glioma.展开更多
Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke,but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in trau...Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke,but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury.In this study we found that,in a mouse model of traumatic brain injury induced by controlled cortical impact,phosphatase actin regulatory factor 1 expression is increased in endothelial cells,neurons,astrocytes,and microglia.When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice,the water content of the brain tissue increased.However,when phosphatase actin regulatory factor 1 was knocked down,the water content decreased.We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway,decreased blood-brain barrier permeability,reduced aquaporin 4 and intercellular adhesion molecule 1 expression,inhibited neuroinflammation,and neuronal apoptosis,thereby improving neurological function.The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury.展开更多
Objective This meta-analysis explored whether the expression of actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)is related to the prognosis and clinicopathological features of patients with cancer.Method...Objective This meta-analysis explored whether the expression of actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)is related to the prognosis and clinicopathological features of patients with cancer.Methods PubMed,EMBASE,and Cochrane Library were systematically searched.Hazard ratios(HRs)with 95%confidence intervals(CIs)were used to assess the prognostic value based on overall survival(OS),disease-free survival(DFS),and progression-free survival(PFS).Odds ratios(ORs)with 95%CIs were used to determine the relationships between AFAP1-AS1 and clinicopathological features,such as large tumor size(LTS),high tumor stage(HTS),poor histological grade(PHG),lymph node metastasis(LNM),and distant metastasis(DM).Results Thirty-five eligible articles and 3433 cases were analyzed.High AFAP1-AS1 expression,compared to low AFAP1-AS1 expression,correlated with significantly shorter OS(HR=2.15,95%CI=1.97-2.34,P<0.001),DFS(HR=1.37,95%CI=1.19-1.57,P<0.001),and PFS(HR=1.97,95%CI=1.56-2.50,P<0.001)in patients with cancer.In various cancers,elevated AFAP1-AS1 expression was significantly associated with LTS(OR=2.76,95%CI=2.16-3.53,P<0.001),HTS(OR=2.23,95%CI=1.83-2.71,P<0.001),and PHG(OR=1.39,95%CI=1.08-1.79,P=0.01)but not LNM(OR=1.59,95%CI=0.88-2.85,P=0.12)or DM(OR=1.81,95%CI=0.90-3.66,P=0.10).Conclusion High AFAP1-AS1 expression was associated with prognostic and clinicopathological features,suggesting that AFAP1-AS1 is a prognostic biomarker for human cancers.展开更多
Background:Long non-coding RNA(lncRNA)actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs(miRs)to play cancer...Background:Long non-coding RNA(lncRNA)actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs(miRs)to play cancer-promoting roles in cancer stem cells.However,the regulatory mechanism of AFAP1-AS1 in cervical cancer(CC)stem cells is unknown.The present study aimed to provide a new therapeutic target for the clinical treatment of CC.Methods:Hyaluronic acid receptor cluster of differentiation 44 variant exon 6(CD44v6)(+)CC cells were isolated by flow cytometry(FCM).Small interfering RNAs of AFAP1-AS1(siAFAP1-AS1)were transfected into the(CD44v6)(+)cells.The levels of AFAP1-AS1 were measured by quantitative real-time PCR(qRT-PCR).Sphere formation assay,cell cycle analysis,and Western blotting were used to detect the effect of siAFAP1-AS1.RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor(VEGF)-C.Results:CD44v6(+)CCcells had remarkable stemness and a high level ofAFAP1-AS1.However,AFAP1-AS1knockdownwithsiAFAP1-AS1suppressed the cell cycle transitionofG(1)/S phase and inhibited self-renewal ofCD44v6(+)CCcells,the levels of the stemnessmarkers octamer-binding transcription factor 4(OCT4),osteopontin(OPN),and cluster of differentiation 133(CD133),and the epithelialmesenchymal transition(EMT)-related proteins Twist1,matrix metalloprotease(MMP)-9,and VEGF-C.In the mechanism study,miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+)CC cells.Conclusions:LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.展开更多
基金supported by the National Natural Science Foundation(82073850)the Hunan Provincial Youth Science Foundation Project(2019JJ50964),China.
文摘Objective:Actin filament-associated protein 1 like 1(AFAP1L1)is an adaptor protein lacking enzymatic and transcriptional activity,but the AFAP1L1 gene functions as an oncogene in colorectal cancer and gastric cancers.This study aims to investigate the role of AFAP1L1 in glioma and to explore changes in AFAP1L1 expression during glioma progression.Methods:Clinical and transcriptomic data of glioma patients were downloaded from The Cancer Genome Atlas(TCGA),the Chinese Glioma Genome Atlas(CGGA),and the Gene Expression Omnibus(GEO)databases to analyze the associations between AFAP1L1 expression and glioma prognosis,somatic mutations,immune cell infiltration,and enriched signaling pathways.Western blotting and real-time polymerase chain reaction(PCR)were used to detect AFAP1L1 messenger RNA(mRNA)and protein expression in glioma patients.Results:Patients with high AFAP1L1 expression had poorer prognosis,and AFAP1L1 was identified as an independent risk factor for glioma.In addition,glioma patients with high AFAP1L1 expression exhibited lower levels of somatic mutations,including amplification of oncogenes such as epidermal growth factor receptor and deletion of tumor suppressor genes such as cyclin-dependent kinase inhibitor 2A(CDKN2A).Estimation of STromal and Immune cells in Malignant Tumours using Expression(ESTIMATE)algorithm analysis showed that AFAP1L1 expression was positively correlated with the immune microenvironment.Tumor immune dysfunction and exclusion(TIDE)analysis indicated that glioma patients with high AFAP1L1 expression responded poorly to immunotherapy.Single cell analysis showed that AFAP1L1 expression was mainly concentrated in glioma cells.Enrichment analysis suggested that AFAP1L1 was potentially associated with small guanosine triphosphatases(GTPases),hypoxia-inducible factor-1(HIF-1),focal adhesion,and mitogen-activated protein kinase(MAPK)signaling pathways.Conclusion:AFAP1L1 is a novel biomarker indicating glioma progression and a potential therapeutic target for glioma.
基金supported by the National Natural Science Foundation of China,Nos.81501048(to JD),81801236(to ZMX),81974189(to HLT)Shanghai 6th People’s Hospital Research Fund,No.ynlc201808(to JD).
文摘Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke,but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury.In this study we found that,in a mouse model of traumatic brain injury induced by controlled cortical impact,phosphatase actin regulatory factor 1 expression is increased in endothelial cells,neurons,astrocytes,and microglia.When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice,the water content of the brain tissue increased.However,when phosphatase actin regulatory factor 1 was knocked down,the water content decreased.We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway,decreased blood-brain barrier permeability,reduced aquaporin 4 and intercellular adhesion molecule 1 expression,inhibited neuroinflammation,and neuronal apoptosis,thereby improving neurological function.The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury.
基金Supported by a grant from the“Ten Thousand Plan”Youth Talent Project in Yunnan Province(no grant number is applicable).
文摘Objective This meta-analysis explored whether the expression of actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)is related to the prognosis and clinicopathological features of patients with cancer.Methods PubMed,EMBASE,and Cochrane Library were systematically searched.Hazard ratios(HRs)with 95%confidence intervals(CIs)were used to assess the prognostic value based on overall survival(OS),disease-free survival(DFS),and progression-free survival(PFS).Odds ratios(ORs)with 95%CIs were used to determine the relationships between AFAP1-AS1 and clinicopathological features,such as large tumor size(LTS),high tumor stage(HTS),poor histological grade(PHG),lymph node metastasis(LNM),and distant metastasis(DM).Results Thirty-five eligible articles and 3433 cases were analyzed.High AFAP1-AS1 expression,compared to low AFAP1-AS1 expression,correlated with significantly shorter OS(HR=2.15,95%CI=1.97-2.34,P<0.001),DFS(HR=1.37,95%CI=1.19-1.57,P<0.001),and PFS(HR=1.97,95%CI=1.56-2.50,P<0.001)in patients with cancer.In various cancers,elevated AFAP1-AS1 expression was significantly associated with LTS(OR=2.76,95%CI=2.16-3.53,P<0.001),HTS(OR=2.23,95%CI=1.83-2.71,P<0.001),and PHG(OR=1.39,95%CI=1.08-1.79,P=0.01)but not LNM(OR=1.59,95%CI=0.88-2.85,P=0.12)or DM(OR=1.81,95%CI=0.90-3.66,P=0.10).Conclusion High AFAP1-AS1 expression was associated with prognostic and clinicopathological features,suggesting that AFAP1-AS1 is a prognostic biomarker for human cancers.
文摘Background:Long non-coding RNA(lncRNA)actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs(miRs)to play cancer-promoting roles in cancer stem cells.However,the regulatory mechanism of AFAP1-AS1 in cervical cancer(CC)stem cells is unknown.The present study aimed to provide a new therapeutic target for the clinical treatment of CC.Methods:Hyaluronic acid receptor cluster of differentiation 44 variant exon 6(CD44v6)(+)CC cells were isolated by flow cytometry(FCM).Small interfering RNAs of AFAP1-AS1(siAFAP1-AS1)were transfected into the(CD44v6)(+)cells.The levels of AFAP1-AS1 were measured by quantitative real-time PCR(qRT-PCR).Sphere formation assay,cell cycle analysis,and Western blotting were used to detect the effect of siAFAP1-AS1.RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor(VEGF)-C.Results:CD44v6(+)CCcells had remarkable stemness and a high level ofAFAP1-AS1.However,AFAP1-AS1knockdownwithsiAFAP1-AS1suppressed the cell cycle transitionofG(1)/S phase and inhibited self-renewal ofCD44v6(+)CCcells,the levels of the stemnessmarkers octamer-binding transcription factor 4(OCT4),osteopontin(OPN),and cluster of differentiation 133(CD133),and the epithelialmesenchymal transition(EMT)-related proteins Twist1,matrix metalloprotease(MMP)-9,and VEGF-C.In the mechanism study,miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+)CC cells.Conclusions:LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.
