Loss of ARID1A promotes proliferation, migration and invasion via the Akt signaling pathway in NPC
Received 1 March 2019
Accepted for publication 10 May 2019
Published 29 May 2019 Volume 2019:11 Pages 4931—4946
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Alexandra R. Fernandes
Yang Yang,1,* Xiaoyu Wang,1,* Junjun Yang,2 Jingling Duan,1 Zhen Wu,3 Fan Yang,1 Xiaoling Zhang,4 Shengjun Xiao1
1Department of Pathology, the Second Affiliated Hospital, Guilin Medical University, Guilin 541199, People’s Republic of China; 2Department of Stomatology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, People’s Republic of China; 3Xiangya Medical College of South Central University, Changsha 413000, People’s Republic of China; 4Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin 541199, People’s Republic of China
*These authors contributed equally to this work
Background: AT-rich interactive domain-containing protein 1A (ARID1A) is a member of the switch/sucrose nonfermentable chromatin remodeling complex, which has been observed to be mutated in various tumors. The loss of ARID1A is reported to be frequently associated with PI3K/Akt pathway activation.
Objective: The roles of ARID1A in nasopharyngeal carcinoma (NPC) have not been reported until now. The aim of this research was to explore the clinical significance and potential mechanism of ARID1A in NPC development and progression.
Methods: ARID1A expression levels were investigated in human NPC tissues and cell lines. The effects of ARID1A knockdown on nasopharyngeal cancer cell proliferation, migration and invasion were evaluated in vitro using CCK8, wound healing, transwell and flow cytometry assays. The expression of relevant proteins was evaluated by Western blot assays.
Results: In this study, ARID1A was significantly downregulated in NPC tissues and cells. Furthermore, low ARID1A expression was significantly associated with aggressive clinicopathological characteristics and poor survival in NPC patients. Depletion of endogenous ARID1A by siRNA promoted proliferation, migration and invasion in CNE1 and HNE1 cells. Additionally, ARID1A knockdown increased the phosphorylation of Akt in NPC cells. High levels of p-Akt were also observed in NPC biopsies and correlated with ARID1A downregulation. These results imply that the loss of ARID1A could activate Akt signaling. In addition, MK-2206 (a highly selective inhibitor of Akt) partially suppressed NPC cell proliferation, migration and invasion, which were induced by ARID1A knockdown.
Conclusion: Our findings indicate that ARID1A plays an essential role in modulating the Akt pathway, functions as a tumor suppressor in NPC and may be a potential target for NPC treatment.
Keywords: nasopharyngeal carcinoma, SWI/SNF, ARID1A, PI3K/Akt pathway, Akt inhibitor
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]