Cargando…

LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma

Nucleolar and spindle-associated protein 1 (NUSAP1) is a potential molecular marker and intervention target for glioblastoma (GBM). In this study, we aim to investigate upstream regulatory lncRNAs and miRNAs of NUSAP1 through both experimental and bioinformatic methods. We screened upstream lncRNAs...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Deheng, Hu, Junda, Li, Sen, Zhou, Changshuai, Feng, Mingtao, Li, Liangdong, Gao, Yang, Chen, Xin, Wu, Xiaojun, Cao, Yiqun, Hao, Bin, Chen, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056594/
https://www.ncbi.nlm.nih.gov/pubmed/36982952
http://dx.doi.org/10.3390/ijms24065878
_version_ 1785016161145978880
author Li, Deheng
Hu, Junda
Li, Sen
Zhou, Changshuai
Feng, Mingtao
Li, Liangdong
Gao, Yang
Chen, Xin
Wu, Xiaojun
Cao, Yiqun
Hao, Bin
Chen, Lei
author_facet Li, Deheng
Hu, Junda
Li, Sen
Zhou, Changshuai
Feng, Mingtao
Li, Liangdong
Gao, Yang
Chen, Xin
Wu, Xiaojun
Cao, Yiqun
Hao, Bin
Chen, Lei
author_sort Li, Deheng
collection PubMed
description Nucleolar and spindle-associated protein 1 (NUSAP1) is a potential molecular marker and intervention target for glioblastoma (GBM). In this study, we aim to investigate upstream regulatory lncRNAs and miRNAs of NUSAP1 through both experimental and bioinformatic methods. We screened upstream lncRNAs and miRNAs of NUSAP1 through multiple databases based on ceRNA theory. Then, in vitro and in vivo experiments were performed to elucidate the relevant biological significance and regulatory mechanism among them. Finally, the potential downstream mechanism was discussed. LINC01393 and miR-128-3p were screened as upstream regulatory molecules of NUSAP1 by TCGA and ENCORI databases. The negative correlations among them were confirmed in clinical specimens. Biochemical studies revealed that overexpression or knockdown of LINC01393 respectively enhanced or inhibited malignant phenotype of GBM cells. MiR-128-3p inhibitor reversed LINC01393 knockdown-mediated impacts on GBM cells. Then, dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to validate LINC01393/miR-128-3p/NUSAP1 interactions. In vivo, LINC01393-knockdown decreased tumor growth and improved mice survival, while restoration of NUSAP1 partially reversed these effects. Additionally, enrichment analysis and western blot revealed that the roles of LINC01393 and NUSAP1 in GBM progression were associated with NF-κB activation. Our findings showed that LINC01393 sponged miR-128-3p to upregulate NUSAP1, thereby promoting GBM development and progression via activating NF-κB pathway. This work deepens understanding of GBM mechanisms and provides potential novel therapeutic targets for GBM.
format Online
Article
Text
id pubmed-10056594
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100565942023-03-30 LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma Li, Deheng Hu, Junda Li, Sen Zhou, Changshuai Feng, Mingtao Li, Liangdong Gao, Yang Chen, Xin Wu, Xiaojun Cao, Yiqun Hao, Bin Chen, Lei Int J Mol Sci Article Nucleolar and spindle-associated protein 1 (NUSAP1) is a potential molecular marker and intervention target for glioblastoma (GBM). In this study, we aim to investigate upstream regulatory lncRNAs and miRNAs of NUSAP1 through both experimental and bioinformatic methods. We screened upstream lncRNAs and miRNAs of NUSAP1 through multiple databases based on ceRNA theory. Then, in vitro and in vivo experiments were performed to elucidate the relevant biological significance and regulatory mechanism among them. Finally, the potential downstream mechanism was discussed. LINC01393 and miR-128-3p were screened as upstream regulatory molecules of NUSAP1 by TCGA and ENCORI databases. The negative correlations among them were confirmed in clinical specimens. Biochemical studies revealed that overexpression or knockdown of LINC01393 respectively enhanced or inhibited malignant phenotype of GBM cells. MiR-128-3p inhibitor reversed LINC01393 knockdown-mediated impacts on GBM cells. Then, dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to validate LINC01393/miR-128-3p/NUSAP1 interactions. In vivo, LINC01393-knockdown decreased tumor growth and improved mice survival, while restoration of NUSAP1 partially reversed these effects. Additionally, enrichment analysis and western blot revealed that the roles of LINC01393 and NUSAP1 in GBM progression were associated with NF-κB activation. Our findings showed that LINC01393 sponged miR-128-3p to upregulate NUSAP1, thereby promoting GBM development and progression via activating NF-κB pathway. This work deepens understanding of GBM mechanisms and provides potential novel therapeutic targets for GBM. MDPI 2023-03-20 /pmc/articles/PMC10056594/ /pubmed/36982952 http://dx.doi.org/10.3390/ijms24065878 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Deheng
Hu, Junda
Li, Sen
Zhou, Changshuai
Feng, Mingtao
Li, Liangdong
Gao, Yang
Chen, Xin
Wu, Xiaojun
Cao, Yiqun
Hao, Bin
Chen, Lei
LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma
title LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma
title_full LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma
title_fullStr LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma
title_full_unstemmed LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma
title_short LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma
title_sort linc01393, a novel long non-coding rna, promotes the cell proliferation, migration and invasion through mir-128-3p/nusap1 axis in glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056594/
https://www.ncbi.nlm.nih.gov/pubmed/36982952
http://dx.doi.org/10.3390/ijms24065878
work_keys_str_mv AT lideheng linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT hujunda linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT lisen linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT zhouchangshuai linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT fengmingtao linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT liliangdong linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT gaoyang linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT chenxin linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT wuxiaojun linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT caoyiqun linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT haobin linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma
AT chenlei linc01393anovellongnoncodingrnapromotesthecellproliferationmigrationandinvasionthroughmir1283pnusap1axisinglioblastoma