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Expression and biological function of rhotekin in gastric cancer through regulating p53 pathway

Authors Sun MY, Zhang H, Tao J, Ni ZH, Wu QX, Tang QF

Received 25 August 2018

Accepted for publication 10 December 2018

Published 25 January 2019 Volume 2019:11 Pages 1069—1080

DOI https://doi.org/10.2147/CMAR.S185345

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Meng-Yao Sun,1,* Hong Zhang,2,* Jie Tao,1 Zhen-Hua Ni,1 Qiu-Xue Wu,1 Qing-Feng Tang1

1Department of Clinical Laboratory and Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; 2Center for Innovative Chinese Medicine Research, Institute of Interdisciplinary Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

*These authors contributed equally to this work

Background/aim: Gastric cancer (GC) is one of a most threatening cancer globally. Rhotekin (RTKN), a Rho effector, has been reported to be upregulated in GC tissues. This study aimed to investigate the underlying regulatory roles of RTKN in the biological behavior of GC.
Methods: Real-time PCR and Western blotting were carried out to detect the mRNA and protein expression, respectively. Cell Counting Kit-8 and xenograft nude mice model were used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell cycle distribution and cell apoptosis.
Results: RTKN had high expression level in GC compared with normal tissues. RTKN expression strongly associated with tumor size, TNM stage, lymphnode metastasis and the poor prognosis of patients with GC. Downregulation of RTKN significantly repressed GC cell proliferation, but increased cell population in G1/S phase and induced cell apoptosis. Moreover, the RTKN expression level was related to the p53 signaling pathway and histone deacetylase (HDAC) Class I pathway. RTKN knockdown caused a notable increment in the acetylation level of p53 (Lys382), and the expression of p53-target genes (p21, Bax, and PUMA), as well as a reduction in the expression of a potential deacetylase for p53, HDAC1. Notably, downregulation of HDAC1 had similar effects as RTKN knockdown, and RTKN overexpression could hardly abrogate the effects of HDAC1 knockdown on GC cells.
Conclusion: RTKN could work as an oncogene via regulating HDAC1/p53 and may become a promising treatment strategy for GC.

Keywords: RTKN, gastric cancer, proliferation, invasion, HDAC1/p53


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