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Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer

Lung cancer is a malignant tumour type with the highest morbidity and mortality, and non-small-cell lung cancer (NSCLC) is the most common pathological type. GINS complex subunit 2 (GINS2) is a member of the GINS family and is closely related to DNA replication and damage, participates in cell cycle...

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Autores principales: Chi, Feng, Wang, Zhou, Li, Yuzhu, Chang, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133113/
https://www.ncbi.nlm.nih.gov/pubmed/32181475
http://dx.doi.org/10.1042/BSR20193949
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author Chi, Feng
Wang, Zhou
Li, Yuzhu
Chang, Ning
author_facet Chi, Feng
Wang, Zhou
Li, Yuzhu
Chang, Ning
author_sort Chi, Feng
collection PubMed
description Lung cancer is a malignant tumour type with the highest morbidity and mortality, and non-small-cell lung cancer (NSCLC) is the most common pathological type. GINS complex subunit 2 (GINS2) is a member of the GINS family and is closely related to DNA replication and damage, participates in cell cycle regulation and plays a key role in cell proliferation and apoptosis. In the present study, we aimed to explore the role and underlying molecular mechanism of GINS2 in the development of NSCLC. The results showed that GINS2 is significantly increased in NSCLC tissues and cell lines. Knockdown of GINS2 significantly decreases cell proliferation, causing G(2)/M phase cell cycle arrest. Knockdown of GINS2 reverses the effect of nocodazole on the levels of cyclin-dependent kinase 1 (CDK1) and cyclin-B1. Meanwhile, knockdown of GINS2 significantly elevates the apoptosis rate and apoptosis-related protein Bax and decreases Bcl-2. In addition, GINS2 knockdown induces an increase in the levels of p53 and growth arrest and DNA damage 45A (GADD45A). Co-transfection with GINS2-siRNA and siRNA against p53 (p53-siRNA) or co-transfection with GINS2-siRNA and siRNA against GADD45A (GADD45A-siRNA) partially reverses the effects of GINS2 knockdown on cell proliferation and apoptosis. Taken together, these results indicate that GINS2 knockdown down-regulates cell proliferation, induces G2/M phase cell cycle arrest and increases apoptosis, possibly through the p53/GADD45A pathway.
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spelling pubmed-71331132020-04-08 Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer Chi, Feng Wang, Zhou Li, Yuzhu Chang, Ning Biosci Rep Cancer Lung cancer is a malignant tumour type with the highest morbidity and mortality, and non-small-cell lung cancer (NSCLC) is the most common pathological type. GINS complex subunit 2 (GINS2) is a member of the GINS family and is closely related to DNA replication and damage, participates in cell cycle regulation and plays a key role in cell proliferation and apoptosis. In the present study, we aimed to explore the role and underlying molecular mechanism of GINS2 in the development of NSCLC. The results showed that GINS2 is significantly increased in NSCLC tissues and cell lines. Knockdown of GINS2 significantly decreases cell proliferation, causing G(2)/M phase cell cycle arrest. Knockdown of GINS2 reverses the effect of nocodazole on the levels of cyclin-dependent kinase 1 (CDK1) and cyclin-B1. Meanwhile, knockdown of GINS2 significantly elevates the apoptosis rate and apoptosis-related protein Bax and decreases Bcl-2. In addition, GINS2 knockdown induces an increase in the levels of p53 and growth arrest and DNA damage 45A (GADD45A). Co-transfection with GINS2-siRNA and siRNA against p53 (p53-siRNA) or co-transfection with GINS2-siRNA and siRNA against GADD45A (GADD45A-siRNA) partially reverses the effects of GINS2 knockdown on cell proliferation and apoptosis. Taken together, these results indicate that GINS2 knockdown down-regulates cell proliferation, induces G2/M phase cell cycle arrest and increases apoptosis, possibly through the p53/GADD45A pathway. Portland Press Ltd. 2020-04-03 /pmc/articles/PMC7133113/ /pubmed/32181475 http://dx.doi.org/10.1042/BSR20193949 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).
spellingShingle Cancer
Chi, Feng
Wang, Zhou
Li, Yuzhu
Chang, Ning
Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer
title Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer
title_full Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer
title_fullStr Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer
title_full_unstemmed Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer
title_short Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer
title_sort knockdown of gins2 inhibits proliferation and promotes apoptosis through the p53/gadd45a pathway in non-small-cell lung cancer
topic Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133113/
https://www.ncbi.nlm.nih.gov/pubmed/32181475
http://dx.doi.org/10.1042/BSR20193949
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