Dataset Information

LINC00511 contributes to glioblastoma tumorigenesis and epithelial-mesenchymal transition via LINC00511/miR-524-5p/YB1/ZEB1 positive feedback loop.

ABSTRACT: Tumour invasion is closely related to the prognosis and recurrence of glioblastoma multiforme and partially attributes to epithelial-mesenchymal transition. Long intergenic non-coding RNA 00511 (LINC00511) plays a pivotal role in tumour; however, the role of LINC00511 in GBM, especially in the epigenetic molecular regulation mechanism of EMT, is still unclear. Here, we found that LINC00511 was up-regulated in GBM tissues and relatively high LINC00511 expression predicted poorer prognosis. Moreover, ectopic LINC00511 enhanced GBM cells proliferation, EMT, migration and invasion, whereas LINC00511 knockdown had the opposite effects. Mechanistically, we confirmed that ZEB1 acted as a transcription factor for LINC00511 in GBM cells. Subsequently, we found that LINC00511 served as a competing endogenous RNA that sponged miR-524-5p to indirectly regulate YB1, whereas, up-regulated YB1 promoted ZEB1 expression, which inversely facilitated LINC00511 expression. Finally, orthotopic xenograft models were performed to further demonstrate the LINC00511 on GBM tumorigenesis. This study demonstrates that a LINC00511/miR-524-5p/YB1/ZEB1 positive feedback loop provides potential therapeutic targets for GBM progression.

SUBMITTER: Du X

PROVIDER: S-EPMC6991637 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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LINC00511 contributes to glioblastoma tumorigenesis and epithelial-mesenchymal transition via LINC00511/miR-524-5p/YB1/ZEB1 positive feedback loop.

Du Xiaoliu X Tu Yiming Y Liu Shuang S Zhao Pengzhan P Bao Zhongyuan Z Li Chong C Li Jinhao J Pan Minhong M Ji Jing J

Journal of cellular and molecular medicine 20191219 2

Tumour invasion is closely related to the prognosis and recurrence of glioblastoma multiforme and partially attributes to epithelial-mesenchymal transition. Long intergenic non-coding RNA 00511 (LINC00511) plays a pivotal role in tumour; however, the role of LINC00511 in GBM, especially in the epigenetic molecular regulation mechanism of EMT, is still unclear. Here, we found that LINC00511 was up-regulated in GBM tissues and relatively high LINC00511 expression predicted poorer prognosis. Moreov ...[more]

PMID: 31856394

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Project description:BackgroundGlioblastoma is the most common primary malignant intracranial tumor with poor clinical prognosis in adults. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) function as important regulators in cancer progression, including glioblastoma. Here, we identified a new lncRNA LPP antisense RNA-2 (LPP-AS2) and investigated its function and mechanism in the development of glioma.MethodsHigh-throughput RNA sequencing was performed to discriminate differentially expressed lncRNAs and mRNAs between glioma tissues and normal brain tissues. Expression of LPP-AS2, epidermal growth factor receptor (EGFR) and miR-7-5p in glioma tissues and cell lines was detected by real-time quantitative PCR (RT-qPCR), and the functions of lncRNA LPP-AS2 in glioma were assessed by in vivo and in vitro assays. Insight into the underlying mechanism of competitive endogenous RNAs (ceRNAs) was obtained via bioinformatic analysis, dual luciferase reporter assays, RNA pulldown assays, RNA immunoprecipitation (RIP) and rescue experiments.ResultsThe results of high-throughput RNA-seq indicated lncRNA LPP-AS2 was upregulated in glioma tissues and further confirmed by RT-qPCR. Higher LPP-AS2 expression was related to a poor prognosis in glioma patients. Based on functional studies, LPP-AS2 depletion inhibited glioma cell proliferation, invasion and promoted apoptosis in vitro and restrained tumor growth in vivo, overexpression of LPP-AS2 resulted in the opposite effects. In addition, LPP-AS2 and EGFR were observed in co-expression networks. LPP-AS2 was found to function as a ceRNA to regulate EGFR expression by sponging miR-7-5p in glioma cells. The result of chromatin immunoprecipitation (ChIP) assays validated that c-MYC binds directly to the promoter region of LPP-AS2. As a downstream protein of EGFR, c-MYC was modulated by LPP-AS2 and in turn enhanced LPP-AS2 expression. Thus, lncRNA LPP-AS2 promoted glioma tumorigenesis via a miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop.ConclusionsOur study elucidated that LPP-AS2 acted as an oncogene through a novel molecular pathway in glioma and might be a potential therapeutic approach for glioma diagnosis, therapy and prognosis.

Dataset Information

LINC00511 contributes to glioblastoma tumorigenesis and epithelial-mesenchymal transition via LINC00511/miR-524-5p/YB1/ZEB1 positive feedback loop.

Publications

LINC00511 contributes to glioblastoma tumorigenesis and epithelial-mesenchymal transition via LINC00511/miR-524-5p/YB1/ZEB1 positive feedback loop.

Similar Datasets

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