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Knockdown of CCNO decreases the tumorigenicity of gastric cancer by inducing apoptosis

Authors Li L, Cao Y, Zhou H, Li Y, He B, Zhou X, Nie Z, Liang L, Liu Y, Ye L

Received 4 June 2018

Accepted for publication 11 September 2018

Published 26 October 2018 Volume 2018:11 Pages 7471—7481


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Yao Dai

Lan Li,1,2,* Yu Cao,1 Hourong Zhou,2 Yu Li,3 Bing He,1,* Xia Zhou,4 Zhao Nie,5 Li Liang,6 Ying Liu,7 Limin Ye3

1Department of Emergency, West China Hospital, Sichuan University, Chengdu 610041, China; 2Department of General Practice, Guizhou Provincial People’s Hospital, Guiyang 610041, China; 3Department of Gastroenterology, Guizhou Provincial People’s Hospital, Guiyang 610041, China; 4Department of Emergency, Guizhou Provincial People’s Hospital, Guiyang 610041, China; 5Department of Medical Records and Statistics, Guizhou Provincial People’s Hospital, Guiyang 610041, China; 6Medical Department, Guizhou Provincial People’s Hospital, Guiyang 610041, China; 7Department of Emergency, the Hospital affiliated to Southwest Medical University, Sichuan 646000, China

*These authors contributed equally to this work

Purpose: Recently, Cyclin O (CCNO) has been reported to be a novel protein of the cyclin family. However, the clinical significance and functional roles of CCNO in human cancer, including gastric cancer (GC), remain largely unexplored. In this study, we investigated the clinical and functional roles of CCNO in GC.
Methods: We analyzed CCNO expression patterns in GC patients. To investigate the role of CCNO in malignancy of GC, we used lentivirus-delivered short hairpin RNA to knockdown CCNO expression in GC cell lines. Then multiparametric high-content screening and MTT incorporation assay were used to assess the cell proliferation capability. Cell apoptosis was detected by flow cytometry and Caspase 3/7 assays. Furthermore, the effect of CCNO on tumorigenicity of GC was also determined in vivo. Finally, microarray analysis was performed to elucidate the molecular mechanisms by which shCCNO inhibited the malignancy of GC cells.
Results: The analysis from The Cancer Genome Atlas database revealed elevated CCNO mRNA expression in GC tissue than in the adjacent normal tissue. Immunohistochemical studies also showed that stronger cytoplasmic staining of CCNO was detected in GC tissues. Downregulation of CCNO in GC cells efficiently, through infection with the lentivirus-mediated specific short hairpin RNA, could significantly induce cell apoptosis and inhibit the proliferative properties both in vitro and in vivo. Microarray analysis further revealed 652 upregulated genes and 527 downregulated genes in the shCCNO group compared with control, and indicated that CCNO knockdown could inhibit the malignancy of GC cells through inducing genome-wide gene expression changes.
Conclusion: Our work is the first to reveal that elevated CCNO expression is closely associated with human GC development and that CCNO knockdown could efficiently inhibit the malignant properties of GC cells by inducing cell apoptosis. Therefore, CCNO could be used as a potential biomarker for prognosis or even as a therapeutic target in human GC.

Keywords: Cyclin O, gastric cancer, apoptosis, proliferation, tumorigenicity

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