Association of overexpressed MYC gene with altered PHACTR3 and E2F4 genes contributes to non-small cell lung carcinoma pathogenesis

Background: C-Myc is one of the major cellular oncogenes overexpressed in non-small cell lung carcinoma (NSCLC). Its deregulated expression is necessary but not sufficient for malignant transformation. We evaluated expression of MYC gene in NSCLC patients and its association with alterations in the...

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Main Authors: Dragoj Miodrag, Banković Jasna, Podolski-Renić Ana, Stojković-Burić Sonja, Pešić Milica, Tanić Nikola, Stanković Tijana
Format: Article
Language:English
Published: Society of Medical Biochemists of Serbia, Belgrade 2019-01-01
Series:Journal of Medical Biochemistry
Subjects:
Online Access:https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2019/1452-82581902188D.pdf
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author Dragoj Miodrag
Banković Jasna
Podolski-Renić Ana
Stojković-Burić Sonja
Pešić Milica
Tanić Nikola
Stanković Tijana
author_facet Dragoj Miodrag
Banković Jasna
Podolski-Renić Ana
Stojković-Burić Sonja
Pešić Milica
Tanić Nikola
Stanković Tijana
author_sort Dragoj Miodrag
collection DOAJ
description Background: C-Myc is one of the major cellular oncogenes overexpressed in non-small cell lung carcinoma (NSCLC). Its deregulated expression is necessary but not sufficient for malignant transformation. We evaluated expression of MYC gene in NSCLC patients and its association with alterations in the genes previously identified to be related to NSCLC pathogenesis, PHACt R 3 and E2F4. Methods: We analyzed M YC gene expression by qRT-PCR in 30 NSCLC patients' samples and paired normal lung tissue. M YC expression was further statistically evaluated in relation to histopathological parameters, PHACTR3 and E2F4 gene alterations and survival. Alterations in aforementioned genes were previously detected and identified based on AP-PCR profiles of paired normal and tumor DNA samples, selection of DNA bands with altered mobility in tumor samples and their characterization by the reamplification, cloning and sequencing. Results: M YC s significantly increased in NSCLC samples and its overexpression significantly associated with squamous cell carcinoma subtype. Most importantly, MYC overexpression significantly coincided with mutations in PHACTR3 and E2F4 genes, in group of all patients and in squamous cell carcinoma subtype. Moreover, patients with jointly overexpressed M YC and altered PHACTR3 or E2F4 showed trend of shorter survival. Conclusions: Overall, MYC is frequently overexpressed in NSCLC and it is associated with mutated PHACTR3 gene, as well as mutated E2F4 gene. These joint gene alterations could be considered as potential molecular markers of NSCLC and its specific subtypes.
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spelling doaj.art-d49eeaf3a51c4296bb464f48af6d4df02022-12-21T20:36:00ZengSociety of Medical Biochemists of Serbia, BelgradeJournal of Medical Biochemistry1452-82581452-82662019-01-013821881951452-82581902188DAssociation of overexpressed MYC gene with altered PHACTR3 and E2F4 genes contributes to non-small cell lung carcinoma pathogenesisDragoj Miodrag0Banković Jasna1Podolski-Renić Ana2Stojković-Burić Sonja3Pešić Milica4Tanić Nikola5https://orcid.org/0000-0001-5817-7763Stanković Tijana6University of Belgrade, Institute for Biological Research "Siniša Stanković", Department of Neurobiology, BelgradeUniversity of Belgrade, Institute for Biological Research "Siniša Stanković", Department of Neurobiology, BelgradeUniversity of Belgrade, Institute for Biological Research "Siniša Stanković", Department of Neurobiology, BelgradeUniversity of Belgrade, Institute for Biological Research "Siniša Stanković", Department of Neurobiology, BelgradeUniversity of Belgrade, Institute for Biological Research "Siniša Stanković", Department of Neurobiology, BelgradeUniversity of Belgrade, Institute for Biological Research "Siniša Stanković", Department of Neurobiology, BelgradeUniversity of Belgrade, Institute for Biological Research "Siniša Stanković", Department of Neurobiology, BelgradeBackground: C-Myc is one of the major cellular oncogenes overexpressed in non-small cell lung carcinoma (NSCLC). Its deregulated expression is necessary but not sufficient for malignant transformation. We evaluated expression of MYC gene in NSCLC patients and its association with alterations in the genes previously identified to be related to NSCLC pathogenesis, PHACt R 3 and E2F4. Methods: We analyzed M YC gene expression by qRT-PCR in 30 NSCLC patients' samples and paired normal lung tissue. M YC expression was further statistically evaluated in relation to histopathological parameters, PHACTR3 and E2F4 gene alterations and survival. Alterations in aforementioned genes were previously detected and identified based on AP-PCR profiles of paired normal and tumor DNA samples, selection of DNA bands with altered mobility in tumor samples and their characterization by the reamplification, cloning and sequencing. Results: M YC s significantly increased in NSCLC samples and its overexpression significantly associated with squamous cell carcinoma subtype. Most importantly, MYC overexpression significantly coincided with mutations in PHACTR3 and E2F4 genes, in group of all patients and in squamous cell carcinoma subtype. Moreover, patients with jointly overexpressed M YC and altered PHACTR3 or E2F4 showed trend of shorter survival. Conclusions: Overall, MYC is frequently overexpressed in NSCLC and it is associated with mutated PHACTR3 gene, as well as mutated E2F4 gene. These joint gene alterations could be considered as potential molecular markers of NSCLC and its specific subtypes.https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2019/1452-82581902188D.pdfe2f4mycnon-small cell lung carcinomaphactr3
spellingShingle Dragoj Miodrag
Banković Jasna
Podolski-Renić Ana
Stojković-Burić Sonja
Pešić Milica
Tanić Nikola
Stanković Tijana
Association of overexpressed MYC gene with altered PHACTR3 and E2F4 genes contributes to non-small cell lung carcinoma pathogenesis
Journal of Medical Biochemistry
e2f4
myc
non-small cell lung carcinoma
phactr3
title Association of overexpressed MYC gene with altered PHACTR3 and E2F4 genes contributes to non-small cell lung carcinoma pathogenesis
title_full Association of overexpressed MYC gene with altered PHACTR3 and E2F4 genes contributes to non-small cell lung carcinoma pathogenesis
title_fullStr Association of overexpressed MYC gene with altered PHACTR3 and E2F4 genes contributes to non-small cell lung carcinoma pathogenesis
title_full_unstemmed Association of overexpressed MYC gene with altered PHACTR3 and E2F4 genes contributes to non-small cell lung carcinoma pathogenesis
title_short Association of overexpressed MYC gene with altered PHACTR3 and E2F4 genes contributes to non-small cell lung carcinoma pathogenesis
title_sort association of overexpressed myc gene with altered phactr3 and e2f4 genes contributes to non small cell lung carcinoma pathogenesis
topic e2f4
myc
non-small cell lung carcinoma
phactr3
url https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2019/1452-82581902188D.pdf
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