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The miR-142 Suppresses U-87 Glioblastoma Cell Growth by Targeting EGFR Oncogenic Signaling Pathway

Glioblastoma is the most lethal malignancy of the brain and is resistant to conventional cancer treatments. Gene-therapy approaches like using tumor suppressor miRNAs are promising in the treatment of glioblastoma. They control the expression of oncogenes and influence tumor features and behaviors....

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Autores principales: Gheidari, Fatemeh, Arefian, Ehsan, Jamshidi Adegani, Fatemeh, Fallah Atanaki, Fereshteh, Soleimani, Masoud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shaheed Beheshti University of Medical Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842594/
https://www.ncbi.nlm.nih.gov/pubmed/35194440
http://dx.doi.org/10.22037/ijpr.2021.115089.15193
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author Gheidari, Fatemeh
Arefian, Ehsan
Jamshidi Adegani, Fatemeh
Fallah Atanaki, Fereshteh
Soleimani, Masoud
author_facet Gheidari, Fatemeh
Arefian, Ehsan
Jamshidi Adegani, Fatemeh
Fallah Atanaki, Fereshteh
Soleimani, Masoud
author_sort Gheidari, Fatemeh
collection PubMed
description Glioblastoma is the most lethal malignancy of the brain and is resistant to conventional cancer treatments. Gene-therapy approaches like using tumor suppressor miRNAs are promising in the treatment of glioblastoma. They control the expression of oncogenes and influence tumor features and behaviors. Therefore, in the present study, it was predicted that miR-142 regulates oncogenic epidermal growth factor receptor (EGFR) signaling pathway via TargetScan and miRWalk online tools. Its differential expression level was reduced in glioblastoma according to the previous microarray results, and its predicted target genes were upregulated, as shown by the Expression Atlas. The miR-142 was overexpressed in U-87 glioblastoma cells via lentiviral transduction, and the way it influences proliferation and migration of cells was investigated through MTT assay and wound healing assay. Apoptosis rate was also measured via the Annexin V assay, and cell-cycle analysis was done. Then, real-time polymerase chain reaction (real-time PCR) and western blotting were performed to assess fold changes in mRNA and protein levels of the miR-142 predicted targets. Direct target genes of miR-142 were confirmed through a dual-luciferase reporter assay. The miR-142 significantly suppressed cell proliferation and migration and induced apoptosis and cell-cycle arrest in U-87 glioblastoma cells. This was accompanied by a decrease in expression of SHC adaptor protein 4 (SHC4), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), v-akt murine thymoma viral oncogene homolog 1 (AKT1), Kirsten rat sarcoma viral oncogene homolog (KRAS), and mitogen-activated protein kinase 8 (MAPK8) oncogenes at mRNA and protein levels in glioblastoma cells. Also, AKT1 was demonstrated as a direct target of miR-142. Overall, miR-424 acts as tumor suppressor miRNA in glioblastoma cells.
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spelling pubmed-88425942022-02-21 The miR-142 Suppresses U-87 Glioblastoma Cell Growth by Targeting EGFR Oncogenic Signaling Pathway Gheidari, Fatemeh Arefian, Ehsan Jamshidi Adegani, Fatemeh Fallah Atanaki, Fereshteh Soleimani, Masoud Iran J Pharm Res Original Article Glioblastoma is the most lethal malignancy of the brain and is resistant to conventional cancer treatments. Gene-therapy approaches like using tumor suppressor miRNAs are promising in the treatment of glioblastoma. They control the expression of oncogenes and influence tumor features and behaviors. Therefore, in the present study, it was predicted that miR-142 regulates oncogenic epidermal growth factor receptor (EGFR) signaling pathway via TargetScan and miRWalk online tools. Its differential expression level was reduced in glioblastoma according to the previous microarray results, and its predicted target genes were upregulated, as shown by the Expression Atlas. The miR-142 was overexpressed in U-87 glioblastoma cells via lentiviral transduction, and the way it influences proliferation and migration of cells was investigated through MTT assay and wound healing assay. Apoptosis rate was also measured via the Annexin V assay, and cell-cycle analysis was done. Then, real-time polymerase chain reaction (real-time PCR) and western blotting were performed to assess fold changes in mRNA and protein levels of the miR-142 predicted targets. Direct target genes of miR-142 were confirmed through a dual-luciferase reporter assay. The miR-142 significantly suppressed cell proliferation and migration and induced apoptosis and cell-cycle arrest in U-87 glioblastoma cells. This was accompanied by a decrease in expression of SHC adaptor protein 4 (SHC4), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), v-akt murine thymoma viral oncogene homolog 1 (AKT1), Kirsten rat sarcoma viral oncogene homolog (KRAS), and mitogen-activated protein kinase 8 (MAPK8) oncogenes at mRNA and protein levels in glioblastoma cells. Also, AKT1 was demonstrated as a direct target of miR-142. Overall, miR-424 acts as tumor suppressor miRNA in glioblastoma cells. Shaheed Beheshti University of Medical Sciences 2021 /pmc/articles/PMC8842594/ /pubmed/35194440 http://dx.doi.org/10.22037/ijpr.2021.115089.15193 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Gheidari, Fatemeh
Arefian, Ehsan
Jamshidi Adegani, Fatemeh
Fallah Atanaki, Fereshteh
Soleimani, Masoud
The miR-142 Suppresses U-87 Glioblastoma Cell Growth by Targeting EGFR Oncogenic Signaling Pathway
title The miR-142 Suppresses U-87 Glioblastoma Cell Growth by Targeting EGFR Oncogenic Signaling Pathway
title_full The miR-142 Suppresses U-87 Glioblastoma Cell Growth by Targeting EGFR Oncogenic Signaling Pathway
title_fullStr The miR-142 Suppresses U-87 Glioblastoma Cell Growth by Targeting EGFR Oncogenic Signaling Pathway
title_full_unstemmed The miR-142 Suppresses U-87 Glioblastoma Cell Growth by Targeting EGFR Oncogenic Signaling Pathway
title_short The miR-142 Suppresses U-87 Glioblastoma Cell Growth by Targeting EGFR Oncogenic Signaling Pathway
title_sort mir-142 suppresses u-87 glioblastoma cell growth by targeting egfr oncogenic signaling pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842594/
https://www.ncbi.nlm.nih.gov/pubmed/35194440
http://dx.doi.org/10.22037/ijpr.2021.115089.15193
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