Objectives:Glioma,as the most lethal primary brain malignancy with poor prognosis,requires further elucidation on the functional role of long noncoding RNA(lncRNA)DDX11 antisense RNA 1(DDX11-AS1)in its pathogenesis,de...Objectives:Glioma,as the most lethal primary brain malignancy with poor prognosis,requires further elucidation on the functional role of long noncoding RNA(lncRNA)DDX11 antisense RNA 1(DDX11-AS1)in its pathogenesis,despite its established oncogenic functions in other cancers.Therefore,this study sought to characterize the oncogenic role and molecular mechanism of DDX11-AS1 in glioma.Methods:DDX11-AS1 expression levels were analyzed in clinical surgical glioma specimens and publicly available datasets.The functional roles of DDX11-AS1 on glioma cell proliferation and migration were investigated using in vitro knockdown and overexpression assays.In vivo tumor growth was assessed using orthotopic glioma-bearing mouse models.To elucidate the regulatory axis involving DDX11-AS1,miR-1183,and E2F transcription factor 7(E2F7),we performed competitive endogenous RNA(ceRNA)analysis and conducted functional rescue experiments via miR-1183 inhibition.Results:DDX11-AS1 expression was markedly upregulated in clinical glioma specimens.Functionally,DDX11-AS1 knockdown significantly suppressed glioma cell proliferation and migration in vitro,while its overexpression exacerbated these malignant phenotypes.Orthotopic glioma-bearingmouse models confirmed that DDX11-AS1 drives in vivo glioma tumor growth.Mechanistically,DDX11-AS1 functions as a ceRNA by competitively interacting with miR-1183.Critically,inhibition of miR-1183 rescued the suppressive effects of DDX11-AS1 knockdown on glioma tumorigenic phenotypes and restored E2F7 expression levels.Conclusions:This study demonstrates that lncRNA DDX11-AS1 promotes glioma progression by regulating the miR-1183/E2F7 axis,indicating a potential therapeutic target for glioma.展开更多
BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been lin...BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been linked to immune regulation and tumor suppression,yet its specific role in CRC remains poorly understood.AIM To investigate the tumor-suppressive role of LRRC19 in CRC,focusing on cell cycle,immune microenvironment,and chemotherapy response.METHODS Bioinformatics analyses of Gene Expression Omnibus and The Cancer Genome Atlas databases identified differentially expressed genes in CRC.LRRC19 exp-ression was validated in CRC tissues and cell lines by quantitative PCR,immuno-histochemistry,and Western blotting.Functional assays,including proliferation,soft agar colony formation,flow cytometry,and xenograft models,assessed biological effects.Mechanistic studies with dual-luciferase reporter assays,molecular docking,and drug sensitivity testing explored LRRC19’s interaction with the cyclin-dependent kinase 6(CDK6)/E2F1 axis and oxaliplatin(OXA)response.Single-cell sequencing and immune infiltration analyses assessed its impact on the immune microenvironment.RESULTS LRRC19 expression was significantly downregulated in CRC and associated with poor prognosis.Overexpression of LRRC19 inhibited CRC cell proliferation,induced G0/G1 phase arrest,and suppressed tumor growth in vivo.Mechanistically,LRRC19 suppressed CDK6 transcription by downregulating E2F1,leading to cell cycle arrest.Additionally,LRRC19 promoted immune cell infiltration,particularly B cells and CD4+T cells,while decreasing immunosuppressive cells.LRRC19 also sensitized CRC cells to OXA,enhancing chemotherapy efficacy.CONCLUSION LRRC19 suppresses CRC by targeting the CDK6/E2F1 axis,modulating the immune microenvironment,and enhancing chemotherapy sensitivity,making it a promising therapeutic target for precision medicine in CRC.展开更多
文摘目的:探究血清补体C1q/肿瘤坏死因子相关蛋白l(complement C1q/tumor necrosis factor-related protein 1,CTRP1)、E2F转录因子2(E2F transcription factor 2,E2F2)、C反应蛋白(C-reaction protein,CRP)水平与急性胰腺炎患者病情程度及预后的相关性。方法:急性胰腺炎患者95例,根据病情分为轻度组61例和重度组34例,以同期健康体检者95例为对照组。比较上述3组及不同预后患者血清CTRP1、E2F2、CRP水平、急性生理学与慢性健康状况评分系统Ⅱ(acute physiology and chronic health evaluation,APACHEⅡ)评分,分析血清CTRP1、E2F2、CRP水平与患者病情程度、预后及APACHEⅡ评分的相关性,血清CTRP1、E2F2、CRP水平对重度急性胰腺炎的诊断价值。结果:重度组血清CTRP1、E2F2、CRP水平及APACHEⅡ评分高于轻度组、对照组,轻度组高于对照组(均P<0.05)。预后不良患者血清CTRP1、E2F2、CRP水平高于预后良好患者(均P<0.001)。血清CTRP1、E2F2、CRP水平与急性胰腺炎患者病情程度、预后及APACHEⅡ评分呈正相关(P<0.001)。血清CTRP1、E2F2、CRP水平联合检测诊断重度急性胰腺炎算曲线下面积(area under curve,AUC)为0.843,敏感度为79.41%,特异度为80.33%,优于CTRP1、E2F2、CRP单项检测。结论:血清CTRP1、E2F2、CRP水平与急性胰腺炎患者病情程度及预后关系密切,联合检测对病情评估及预后预测具有一定价值。
基金supported by Shenzhen Science and Technology Program(JCYJ20220530152614033,JCYJ20230807142213027)Funding Statement Special Fund for Economic and Technological Development in Longgang District,Shenzhen(LGKCYLWS2023028).
文摘Objectives:Glioma,as the most lethal primary brain malignancy with poor prognosis,requires further elucidation on the functional role of long noncoding RNA(lncRNA)DDX11 antisense RNA 1(DDX11-AS1)in its pathogenesis,despite its established oncogenic functions in other cancers.Therefore,this study sought to characterize the oncogenic role and molecular mechanism of DDX11-AS1 in glioma.Methods:DDX11-AS1 expression levels were analyzed in clinical surgical glioma specimens and publicly available datasets.The functional roles of DDX11-AS1 on glioma cell proliferation and migration were investigated using in vitro knockdown and overexpression assays.In vivo tumor growth was assessed using orthotopic glioma-bearing mouse models.To elucidate the regulatory axis involving DDX11-AS1,miR-1183,and E2F transcription factor 7(E2F7),we performed competitive endogenous RNA(ceRNA)analysis and conducted functional rescue experiments via miR-1183 inhibition.Results:DDX11-AS1 expression was markedly upregulated in clinical glioma specimens.Functionally,DDX11-AS1 knockdown significantly suppressed glioma cell proliferation and migration in vitro,while its overexpression exacerbated these malignant phenotypes.Orthotopic glioma-bearingmouse models confirmed that DDX11-AS1 drives in vivo glioma tumor growth.Mechanistically,DDX11-AS1 functions as a ceRNA by competitively interacting with miR-1183.Critically,inhibition of miR-1183 rescued the suppressive effects of DDX11-AS1 knockdown on glioma tumorigenic phenotypes and restored E2F7 expression levels.Conclusions:This study demonstrates that lncRNA DDX11-AS1 promotes glioma progression by regulating the miR-1183/E2F7 axis,indicating a potential therapeutic target for glioma.
基金Supported by the Natural Science Foundation of Zhejiang Province,No.LY22H160005。
文摘BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been linked to immune regulation and tumor suppression,yet its specific role in CRC remains poorly understood.AIM To investigate the tumor-suppressive role of LRRC19 in CRC,focusing on cell cycle,immune microenvironment,and chemotherapy response.METHODS Bioinformatics analyses of Gene Expression Omnibus and The Cancer Genome Atlas databases identified differentially expressed genes in CRC.LRRC19 exp-ression was validated in CRC tissues and cell lines by quantitative PCR,immuno-histochemistry,and Western blotting.Functional assays,including proliferation,soft agar colony formation,flow cytometry,and xenograft models,assessed biological effects.Mechanistic studies with dual-luciferase reporter assays,molecular docking,and drug sensitivity testing explored LRRC19’s interaction with the cyclin-dependent kinase 6(CDK6)/E2F1 axis and oxaliplatin(OXA)response.Single-cell sequencing and immune infiltration analyses assessed its impact on the immune microenvironment.RESULTS LRRC19 expression was significantly downregulated in CRC and associated with poor prognosis.Overexpression of LRRC19 inhibited CRC cell proliferation,induced G0/G1 phase arrest,and suppressed tumor growth in vivo.Mechanistically,LRRC19 suppressed CDK6 transcription by downregulating E2F1,leading to cell cycle arrest.Additionally,LRRC19 promoted immune cell infiltration,particularly B cells and CD4+T cells,while decreasing immunosuppressive cells.LRRC19 also sensitized CRC cells to OXA,enhancing chemotherapy efficacy.CONCLUSION LRRC19 suppresses CRC by targeting the CDK6/E2F1 axis,modulating the immune microenvironment,and enhancing chemotherapy sensitivity,making it a promising therapeutic target for precision medicine in CRC.
