Back to Journals » OncoTargets and Therapy » Volume 13

Overexpression of Progerin Results in Impaired Proliferation and Invasion of Non-Small Cell Lung Cancer Cells

Authors Hu XT, Song HC, Yu H, Wu ZC, Liu XG, Chen WC

Received 2 November 2019

Accepted for publication 26 February 2020

Published 30 March 2020 Volume 2020:13 Pages 2629—2642

DOI https://doi.org/10.2147/OTT.S237016

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Nicola Silvestris


Xiao-Ting Hu, Hao-Chang Song, Hui Yu, Zu-Chun Wu, Xin-Guang Liu, Wei-Chun Chen

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Dongguan, Guangdong, People’s Republic of China

Correspondence: Wei-Chun Chen; Xin-Guang Liu
Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Dongguan, Guangdong, People’s Republic of China
Tel +86759 22896026
Email chenwchun@126.com; xgliu64@126.com

Purpose: The accumulation of progerin (PG) in patients is responsible for the pathogenesis of Hutchinson-Gilford Progeria Syndrome (HGPS) because it triggers accelerated aging of cells. However, there are few studies on the effects of progerin on tumor cells. Lung cancer is one of the most common malignant cancers with high global morbidity and mortality rates; non-small cell lung cancer accounts for the majority of cases. The purpose of this study was to determine the effects of progerin on A549 cell proliferation, cell cycle, invasion, migration, sensitivity to DNA damaging agents, senescence and apoptosis with a goal of exploring new ideas for lung cancer treatment.
Methods: A549 cells overexpressing progerin (A549-PG) and a corresponding blank control (A549-GFP) were constructed by lentiviral infection. A nuclear staining assay was utilized to detect abnormal nuclear morphology. The proliferation, cell cycle, colony formation, invasion and migration abilities of A549-PG were compared with those of A549-GFP via EdU assays, flow cytometry, colony formation experiments, and Matrigel invasion and migration assays, respectively. SA‐β‐gal staining was used to measure senescence in cells.
Results: The expression of progerin was significantly higher in A549-PG than A549-GFP. About 20% of A549-PG possessed abnormal nuclei. Overexpression of progerin in A549 cells inhibited cell proliferation, migration and invasion, and associated proteins (CDK4, pRB, ANLN, MMP7 and MMP9) were downregulated. DNA damage repair was also impaired. Progerin did not cause cells to senesce, and there was no difference in apoptosis.
Conclusion: A549-PG generated some cellular changes, including the nuclear skeleton, the cell cycle, DNA damage repair, and migration and invasion abilities. Our data indicate that progerin could cause an imbalance in the steady state in A549 cells and increase their sensitivity to chemotherapeutic drugs.

Keywords: A549 lung cancer cells, progerin, cell cycle, invasion, DNA damage


Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]