EGR1 modulated LncRNA HNF1A-AS1 drives glioblastoma progression via miR-22-3p/ENO1 axis

Abstract Accumulating evidences revealed that long noncoding RNAs (lncRNAs) have been participated in cancer malignant progression, including glioblastoma multiforme (GBM). Despite much studies have found the precise biological role in the regulatory mechanisms of GBM, however the molecular mechanis...

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Autores principales: Chunchun Ma, Hongliang Wang, Gang Zong, Jie He, Yuyang Wang, Fan Yang, Zhihao Yang, Erbao Bian, Bing Zhao
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Publicado: Nature Publishing Group 2021
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spelling oai:doaj.org-article:eec1a9628464437f865390b0d7567b972021-11-14T12:12:25ZEGR1 modulated LncRNA HNF1A-AS1 drives glioblastoma progression via miR-22-3p/ENO1 axis10.1038/s41420-021-00734-32058-7716https://doaj.org/article/eec1a9628464437f865390b0d7567b972021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00734-3https://doaj.org/toc/2058-7716Abstract Accumulating evidences revealed that long noncoding RNAs (lncRNAs) have been participated in cancer malignant progression, including glioblastoma multiforme (GBM). Despite much studies have found the precise biological role in the regulatory mechanisms of GBM, however the molecular mechanisms, particularly upstream mechanisms still need further elucidated. RT-QPCR, cell transfection, western blotting and bioinformatic analysis were executed to detect the expression of EGR1, HNF1A-AS1, miR-22-3p and ENO1 in GBM. Cell proliferation assay, colony formation assay, wound healing, migration and invasion assays were performed to detect the malignant characters of GBM cells. The molecular regulation mechanism was confirmed by luciferase reporter assay, ChIP and RIP. Finally, orthotopic mouse models were established to examine the effect of HNF1A-AS1 in vivo. In the current study, we analyzed clinical samples to show that the HNF1A-AS1 expression is upregulated and associated with poor patient survival in GBM. Functional studies revealed that HNF1A-AS1 knockdown markedly inhibits malignant phenotypes of GBM cells, whereas overexpression of HNF1A-AS1 exerts opposite effect. Mechanistically, the transcription factor EGR1 forced the HNF1A-AS1 expression by directly binding the promoter region of HNF1A-AS1. Furthermore, combined bioinformatics analysis with our mechanistic work, using luciferase reporter assays and RIP, we first demonstrated that HNF1A-AS1 functions as a competing endogenous RNA (ceRNA) with miR-22-3p to regulate ENO1 expression in GBM cells. HNF1A-AS1 directly binds to miR-22-3p and significantly inhibits miR-22-3p expression, while ENO1 expression was increased. miR-22-3p inhibitor offsets the HNF1A-AS1 silencing induced suppression in malignant behaviors of GBM cells. ENO1 was verified as a direct target of miR-22-3p and its expression levels was negatively with the prognosis in GBM patients. Taken together, our study illuminated the definite mechanism of HNF1A-AS1 in promoting GBM malignancy, and provided a novel therapeutic target for further clinical application.Chunchun MaHongliang WangGang ZongJie HeYuyang WangFan YangZhihao YangErbao BianBing ZhaoNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
spellingShingle Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
Chunchun Ma
Hongliang Wang
Gang Zong
Jie He
Yuyang Wang
Fan Yang
Zhihao Yang
Erbao Bian
Bing Zhao
EGR1 modulated LncRNA HNF1A-AS1 drives glioblastoma progression via miR-22-3p/ENO1 axis
description Abstract Accumulating evidences revealed that long noncoding RNAs (lncRNAs) have been participated in cancer malignant progression, including glioblastoma multiforme (GBM). Despite much studies have found the precise biological role in the regulatory mechanisms of GBM, however the molecular mechanisms, particularly upstream mechanisms still need further elucidated. RT-QPCR, cell transfection, western blotting and bioinformatic analysis were executed to detect the expression of EGR1, HNF1A-AS1, miR-22-3p and ENO1 in GBM. Cell proliferation assay, colony formation assay, wound healing, migration and invasion assays were performed to detect the malignant characters of GBM cells. The molecular regulation mechanism was confirmed by luciferase reporter assay, ChIP and RIP. Finally, orthotopic mouse models were established to examine the effect of HNF1A-AS1 in vivo. In the current study, we analyzed clinical samples to show that the HNF1A-AS1 expression is upregulated and associated with poor patient survival in GBM. Functional studies revealed that HNF1A-AS1 knockdown markedly inhibits malignant phenotypes of GBM cells, whereas overexpression of HNF1A-AS1 exerts opposite effect. Mechanistically, the transcription factor EGR1 forced the HNF1A-AS1 expression by directly binding the promoter region of HNF1A-AS1. Furthermore, combined bioinformatics analysis with our mechanistic work, using luciferase reporter assays and RIP, we first demonstrated that HNF1A-AS1 functions as a competing endogenous RNA (ceRNA) with miR-22-3p to regulate ENO1 expression in GBM cells. HNF1A-AS1 directly binds to miR-22-3p and significantly inhibits miR-22-3p expression, while ENO1 expression was increased. miR-22-3p inhibitor offsets the HNF1A-AS1 silencing induced suppression in malignant behaviors of GBM cells. ENO1 was verified as a direct target of miR-22-3p and its expression levels was negatively with the prognosis in GBM patients. Taken together, our study illuminated the definite mechanism of HNF1A-AS1 in promoting GBM malignancy, and provided a novel therapeutic target for further clinical application.
format article
author Chunchun Ma
Hongliang Wang
Gang Zong
Jie He
Yuyang Wang
Fan Yang
Zhihao Yang
Erbao Bian
Bing Zhao
author_facet Chunchun Ma
Hongliang Wang
Gang Zong
Jie He
Yuyang Wang
Fan Yang
Zhihao Yang
Erbao Bian
Bing Zhao
author_sort Chunchun Ma
title EGR1 modulated LncRNA HNF1A-AS1 drives glioblastoma progression via miR-22-3p/ENO1 axis
title_short EGR1 modulated LncRNA HNF1A-AS1 drives glioblastoma progression via miR-22-3p/ENO1 axis
title_full EGR1 modulated LncRNA HNF1A-AS1 drives glioblastoma progression via miR-22-3p/ENO1 axis
title_fullStr EGR1 modulated LncRNA HNF1A-AS1 drives glioblastoma progression via miR-22-3p/ENO1 axis
title_full_unstemmed EGR1 modulated LncRNA HNF1A-AS1 drives glioblastoma progression via miR-22-3p/ENO1 axis
title_sort egr1 modulated lncrna hnf1a-as1 drives glioblastoma progression via mir-22-3p/eno1 axis
publisher Nature Publishing Group
publishDate 2021
url https://doaj.org/article/eec1a9628464437f865390b0d7567b97
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