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Rab18 overexpression promotes proliferation and chemoresistance through regulation of mitochondrial function in human gastric cancer

Authors Wu B, Qi R, Liu X, Qian L, Wu Z

Received 11 April 2018

Accepted for publication 10 September 2018

Published 5 November 2018 Volume 2018:11 Pages 7805—7820

DOI https://doi.org/10.2147/OTT.S170829

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati


Binge Wu,1 Rui Qi,2 Xu Liu,2 Lehua Qian,2 Zhongjun Wu1

1Department of General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 2Department of Ophthalmology, The First Affiliated Hospital of Baotou Medical College, Baotou, China

Background: Dysregulation of Rab18 has been implicated in human cancers. However, its clinical significance and biological function in gastric cancer have not been investigated.
Methods: We examined Rab18 expression in gastric cancer tissues using immunohistochemistry. We used SNU-1 and AGS cell lines for plasmid and siRNA transfection respectively. MTT, colony formation assay, cell cycle analysis, matrigel invasion, wound healing assay, AnnexinV/PI analysis and western blotting were used to examine the biological effect and mechanism of Rab18 in gastric cancer cell lines.
Results: Rab18 protein expression was upregulated in gastric cancer tissues and this correlated with advanced stage and poor prognosis. Rab18 overexpression promoted proliferation in vitro and in vivo. Cell cycle analysis showed that Rab18 overexpression upregulated, while its depletion downregulated S phase percentage. Matrigel invasion and wound healing assays indicated that Rab18 positively regulated SNU-1 cell invasion and migration while its knockdown inhibited AGS cell invasion and migration. Rab18 maintained cell viability and downregulated apoptosis after cisplatin treatment, with upregulated mitochondrial membrane potential and downregulated mitochondrial reactive oxygen species (ROS) production. Rab18 overexpression upregulated p-Rb, survivin while downregulated cytochrome c, cleaved caspase-3 and cleaved PARP.
Conclusion: In conclusion, our results indicate that Rab18 promoted gastric cancer growth and chemoresistance, possibly through regulation of mitochondrial function and survivin.

Keywords: Rab18, gastric cancer, survivin, proliferation, chemoresistance
 

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