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PIK3CA expression in diffuse large B cell lymphoma tissue and the effect of its knockdown in vitro

Authors Cui W, Zheng S, Liu Z, Wang W, Cai Y, Bi R, Cao B, Zhou X

Received 11 December 2016

Accepted for publication 22 March 2017

Published 20 April 2017 Volume 2017:10 Pages 2239—2247

DOI https://doi.org/10.2147/OTT.S129970

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 2

Editor who approved publication: Dr Chiung-Kuei Huang

Wenli Cui,1–4,* Shutao Zheng,5,6,* Zebing Liu,1–3 Weige Wang,1–3 Ying Cai,1–3 Rui Bi,1–3 Bing Cao,1–3 Xiaoyan Zhou1–3

1Department of Pathology, Shanghai Cancer Center, Fudan University, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Institute of Pathology, Fudan University, Shanghai, 4Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, 5Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, 6State Key Lab Incubation Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China

*These authors contributed equally to this work

Abstract: PIK3CA has been extensively investigated from its molecular mechanism perspective and epidemiological association with its mutations in different types of cancers. However, little has been reported regarding the clinicopathological significance of PIK3CA expression in diffuse large B cell lymphoma (DLBCL). In the present study, we investigated the clinicopathological significance of PIK3CA in DLBCL by performing immunohistochemical evaluation of PIK3CA in tissue microarrays consisting of 199 cases of DLBCL. Kaplan–Meier survival analysis was performed to analyze the association between PIK3CA expression and overall prognosis. To further investigate the role of PIK3CA mediated in the proliferation, cell cycle and apoptosis of DLBCL cells, Cell Counting Kit-8 (CCK-8) and flow cytometry assays were carried out in DLBCL cell lines after successful, stable knockdown of PIK3CA using lentiviral short hairpin RNA inference. Our results indicated that although PIK3CA was shown to be extensively expressed in DLBCL, no significant association was observed between PIK3CA expression and clinical outcome or between PIK3CA expression and other clinicopathological parameters, except between performance state (PS) and phosphorylated AKT (p-AKT) expression. In vitro studies revealed that in DLBCL cell lines OCI-LY8 and OCI-LY1, knockdown of PIK3CA could significantly reduce proliferation and promote apoptosis in a G1-phase arrested manner. Additionally, p27 was shown to be markedly upregulated, whereas p-AKT and cyclin D1 were found to be pronouncedly downregulated after stable knockdown of PIK3CA. Together, our results support the oncogenic property of PIK3CA in DLBCL.

Keywords:
diffuse large B cell lymphoma, PIK3CA, proliferation, prognosis

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