Cargando…

MicroRNA-744-5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2

Glioblastoma (GBM) is the most common malignant primary brain tumor, accounting for ~57% of all gliomas and 48% of all malignant primary central nervous system tumors in the United States. Abnormal expression of the replication factor C subunit 2 (RFC2) gene and microRNA (miR)-744-5p is associated w...

Descripción completa

Detalles Bibliográficos
Autores principales: Fan, Fei, Yao, Dongxiao, Yan, Pengfei, Jiang, Xiaobing, Hu, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227640/
https://www.ncbi.nlm.nih.gov/pubmed/34188710
http://dx.doi.org/10.3892/ol.2021.12869
_version_ 1783712570222313472
author Fan, Fei
Yao, Dongxiao
Yan, Pengfei
Jiang, Xiaobing
Hu, Jie
author_facet Fan, Fei
Yao, Dongxiao
Yan, Pengfei
Jiang, Xiaobing
Hu, Jie
author_sort Fan, Fei
collection PubMed
description Glioblastoma (GBM) is the most common malignant primary brain tumor, accounting for ~57% of all gliomas and 48% of all malignant primary central nervous system tumors in the United States. Abnormal expression of the replication factor C subunit 2 (RFC2) gene and microRNA (miR)-744-5p is associated with tumorigenic characteristics, including cellular proliferation, migration and invasiveness. However, the mechanism underlying the interaction between miR-744-5p and RFC2 in GBM remains unknown. Reverse transcription-quantitative (RT-q) PCR analysis of RFC2 and miR-744-5p was performed using GBM tumor tissues and cells, and the association between miR-744-5p and RFC2 was determined by dual-luciferase reporter assay. Cell Counting Kit 8, 5-bromo-2-deoxyuridine (BrdU), wound-healing and cellular adhesion assays, as well as the detection of caspase-3 activity and western blotting were used to detect cellular proliferation, migration and adhesion, caspase-3 activity, and Bax and Bcl-2 protein expression, respectively, in GBM cells. The results of the present study demonstrated that RFC2 expression was increased in GBM tissues and cell lines. Overexpression of RFC2 promoted cellular proliferation, migration, adhesion and an increase in Bcl-2 protein levels, and suppressed cellular caspase-3 activity and Bax protein expression, while silencing RFC2 resulted in the opposite effect. The effects of miR-744-5p inhibition were similar to those of RFC2 overexpression. Moreover, miR-744-5p was found to target RFC2 in GBM cells, and inhibiting the expression of RFC2 suppressed GBM tumorigenesis. In conclusion, the present study demonstrated that miR-744-5p targets RFC2 and suppresses the progression of GBM by repressing cellular proliferation, migration and Bcl-2 protein expression, and effectively promoting caspase-3 activity and Bax protein expression. These findings suggest a new target for the clinical treatment and improved prognosis of patients with GBM in the future.
format Online
Article
Text
id pubmed-8227640
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-82276402021-06-28 MicroRNA-744-5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2 Fan, Fei Yao, Dongxiao Yan, Pengfei Jiang, Xiaobing Hu, Jie Oncol Lett Articles Glioblastoma (GBM) is the most common malignant primary brain tumor, accounting for ~57% of all gliomas and 48% of all malignant primary central nervous system tumors in the United States. Abnormal expression of the replication factor C subunit 2 (RFC2) gene and microRNA (miR)-744-5p is associated with tumorigenic characteristics, including cellular proliferation, migration and invasiveness. However, the mechanism underlying the interaction between miR-744-5p and RFC2 in GBM remains unknown. Reverse transcription-quantitative (RT-q) PCR analysis of RFC2 and miR-744-5p was performed using GBM tumor tissues and cells, and the association between miR-744-5p and RFC2 was determined by dual-luciferase reporter assay. Cell Counting Kit 8, 5-bromo-2-deoxyuridine (BrdU), wound-healing and cellular adhesion assays, as well as the detection of caspase-3 activity and western blotting were used to detect cellular proliferation, migration and adhesion, caspase-3 activity, and Bax and Bcl-2 protein expression, respectively, in GBM cells. The results of the present study demonstrated that RFC2 expression was increased in GBM tissues and cell lines. Overexpression of RFC2 promoted cellular proliferation, migration, adhesion and an increase in Bcl-2 protein levels, and suppressed cellular caspase-3 activity and Bax protein expression, while silencing RFC2 resulted in the opposite effect. The effects of miR-744-5p inhibition were similar to those of RFC2 overexpression. Moreover, miR-744-5p was found to target RFC2 in GBM cells, and inhibiting the expression of RFC2 suppressed GBM tumorigenesis. In conclusion, the present study demonstrated that miR-744-5p targets RFC2 and suppresses the progression of GBM by repressing cellular proliferation, migration and Bcl-2 protein expression, and effectively promoting caspase-3 activity and Bax protein expression. These findings suggest a new target for the clinical treatment and improved prognosis of patients with GBM in the future. D.A. Spandidos 2021-08 2021-06-15 /pmc/articles/PMC8227640/ /pubmed/34188710 http://dx.doi.org/10.3892/ol.2021.12869 Text en Copyright: © Fan et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Fan, Fei
Yao, Dongxiao
Yan, Pengfei
Jiang, Xiaobing
Hu, Jie
MicroRNA-744-5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2
title MicroRNA-744-5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2
title_full MicroRNA-744-5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2
title_fullStr MicroRNA-744-5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2
title_full_unstemmed MicroRNA-744-5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2
title_short MicroRNA-744-5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2
title_sort microrna-744-5p inhibits glioblastoma malignancy by suppressing replication factor c subunit 2
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227640/
https://www.ncbi.nlm.nih.gov/pubmed/34188710
http://dx.doi.org/10.3892/ol.2021.12869
work_keys_str_mv AT fanfei microrna7445pinhibitsglioblastomamalignancybysuppressingreplicationfactorcsubunit2
AT yaodongxiao microrna7445pinhibitsglioblastomamalignancybysuppressingreplicationfactorcsubunit2
AT yanpengfei microrna7445pinhibitsglioblastomamalignancybysuppressingreplicationfactorcsubunit2
AT jiangxiaobing microrna7445pinhibitsglioblastomamalignancybysuppressingreplicationfactorcsubunit2
AT hujie microrna7445pinhibitsglioblastomamalignancybysuppressingreplicationfactorcsubunit2