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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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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 |
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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 |
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