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
Objective:Transcription factor E2F7 exerts suppressive transcription effects and was validated as highly expressed in hepatocellular carcinoma(HCC)in our previous study.Based on the correlation between E2F7 and the di...Objective:Transcription factor E2F7 exerts suppressive transcription effects and was validated as highly expressed in hepatocellular carcinoma(HCC)in our previous study.Based on the correlation between E2F7 and the dismal clinicopathological features in patients,we investigated the downstream regulators controlled by E2F7 in HCC progression and identified a potential E2F7/miR-218-5p axis facilitating HCC cell growth by stabilizing USP32,one of the important ubiquitin-specific peptidases.Methods:The expression profiles of miR-218-5p and USP32 were detected in HCC cell lines and patients’specimens,combined with the analysis of the public databases.The clinicopathological features of 95 HCC patients were analyzed.Cellular functional experiments through the expression regulation of these genes were conducted in vitro.The chromatin immunoprecipitation and the Dual-luciferase reporter assays were carried out to demonstrate the interaction between the candidate genes.-Results:USP32 was aberrantly overexpressed in HCC,and its high expression was positively associated with poor clinical outcomes and served as an independent risk factor.USP32 depletion impaired HCC cell growth and miR218-5p targeted USP32 mRNA,thereby acting as a suppressive upstream regulator in HCC.E2F7 directly binds to the promoter region of miR-218-5p and suppressively modulates the transcription activity.Modulation of the E2F7/miR-218-5p axis significantly impacts USP32 transcription and HCC cell growth.-Conclusions:USP32 is a pivotal ubiquitin peptidase highly expressed in HCC and facilitates tumor development.The E2F7/miR-218-5p axis functions as an upstream regulatory mechanism that modulates USP32 expression through transcriptional suppression.These genes provide the possibility for innovative targets against HCC.展开更多
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 National Natural Science Foundation of China(Nos.82372603 and 82172900)Shanghai Leading Talent Program of Eastern Talent Plan(No.BJJY2024068)+2 种基金Chinese Society of Clinical Oncology(CSCO)-Chaoyang Oncology Research Foundation(No.Y-Young2021-0015)Research Physician Project from Shanghai Jiao Tong University School of Medicine(No.20191901)Shanghai Pujiang Talent Project,China(No.18PJD029).
文摘Objective:Transcription factor E2F7 exerts suppressive transcription effects and was validated as highly expressed in hepatocellular carcinoma(HCC)in our previous study.Based on the correlation between E2F7 and the dismal clinicopathological features in patients,we investigated the downstream regulators controlled by E2F7 in HCC progression and identified a potential E2F7/miR-218-5p axis facilitating HCC cell growth by stabilizing USP32,one of the important ubiquitin-specific peptidases.Methods:The expression profiles of miR-218-5p and USP32 were detected in HCC cell lines and patients’specimens,combined with the analysis of the public databases.The clinicopathological features of 95 HCC patients were analyzed.Cellular functional experiments through the expression regulation of these genes were conducted in vitro.The chromatin immunoprecipitation and the Dual-luciferase reporter assays were carried out to demonstrate the interaction between the candidate genes.-Results:USP32 was aberrantly overexpressed in HCC,and its high expression was positively associated with poor clinical outcomes and served as an independent risk factor.USP32 depletion impaired HCC cell growth and miR218-5p targeted USP32 mRNA,thereby acting as a suppressive upstream regulator in HCC.E2F7 directly binds to the promoter region of miR-218-5p and suppressively modulates the transcription activity.Modulation of the E2F7/miR-218-5p axis significantly impacts USP32 transcription and HCC cell growth.-Conclusions:USP32 is a pivotal ubiquitin peptidase highly expressed in HCC and facilitates tumor development.The E2F7/miR-218-5p axis functions as an upstream regulatory mechanism that modulates USP32 expression through transcriptional suppression.These genes provide the possibility for innovative targets against HCC.
