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Published on: October 4, 2019
Competitive Sequestration of miR-1183 by lncRNA DDX11-AS1 Drives Gliomagenesis through E2F7 Activation
Jianwei Wang1,2, Xinzhi Yang3, Lvbiao Lin4
1Department of Neurosurgery, Shenzhen Hospital, Southern Medical University, Shenzhen, 518100, China.
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-bearing mouse 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.
Insights
Long noncoding RNA DDX11-AS1 promotes glioma progression by activating the miR-1183/E2F7 pathway. This finding highlights DDX11-AS1 as a potential therapeutic target for treating this lethal brain malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioma is a lethal primary brain malignancy with a poor prognosis.
- The role of long noncoding RNA (lncRNA) DDX11-AS1 in glioma pathogenesis requires further investigation.
- DDX11-AS1 has known oncogenic functions in other cancer types.
Purpose of the Study:
- To characterize the oncogenic role of DDX11-AS1 in glioma.
- To elucidate the molecular mechanism by which DDX11-AS1 contributes to glioma progression.
Main Methods:
- Analyzed DDX11-AS1 expression in clinical glioma specimens and public datasets.
- Investigated the functional impact of DDX11-AS1 on glioma cell proliferation and migration using in vitro knockdown and overexpression.
- Assessed in vivo tumor growth in orthotopic glioma mouse models.
- Performed competitive endogenous RNA (ceRNA) analysis to identify regulatory axes involving DDX11-AS1, miR-1183, and E2F7.
- Conducted functional rescue experiments via miR-1183 inhibition.
Main Results:
- DDX11-AS1 expression was significantly upregulated in clinical glioma specimens.
- DDX11-AS1 knockdown suppressed glioma cell proliferation and migration in vitro, while overexpression enhanced these phenotypes.
- In vivo studies confirmed DDX11-AS1 drives glioma tumor growth.
- DDX11-AS1 acts as a ceRNA by interacting with miR-1183.
- miR-1183 inhibition rescued the effects of DDX11-AS1 knockdown on glioma phenotypes and restored E2F7 expression.
Conclusions:
- lncRNA DDX11-AS1 promotes glioma progression through the miR-1183/E2F7 axis.
- DDX11-AS1 represents a potential therapeutic target for glioma treatment.
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