Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2020; 26(1): 21-34
Published online Jan 7, 2020. doi: 10.3748/wjg.v26.i1.21
Feedback regulation between phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 and transforming growth factor β1 and prognostic value in gastric cancer
Qi Shao, Zhi-Ming Chen
Qi Shao, Zhi-Ming Chen, Department of Chemotherapy/Radiotherapy, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Author contributions: Shao Q conducted the experiments and data analysis and drafted the manuscript; Chen ZM designed the project and revised the manuscript.
Institutional review board statement: This study was approved by the Ethics Committee of Affiliated Hospital of Nantong University.
Institutional animal care and use committee statement: This study does not include the animal experiments, so the institutional animal care use statement is not applicable to this manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: The bioinformatic data comes from the public databases, and no additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zhi-Ming Chen, MSc, Doctor, Department of Radiotherapy, Affiliated Hospital of Nantong University, No. 10 Xisi Road, Nantong 226001, Jiangsu Province, China. czm614@163.com
Received: November 26, 2019
Peer-review started: November 26, 2019
First decision: December 12, 2019
Revised: December 15, 2019
Accepted: December 22, 2019
Article in press: December 22, 2019
Published online: January 7, 2020
Abstract
BACKGROUND

Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 (PREX1) was reported to be overexpressed in some cancers and involved in cancer development, but its expression and significance in gastric cancer remain unclear.

AIM

To evaluate the expression of PREX1 in gastric cancer and its significance in the development of gastric cancer, especially to evaluate the potential mechanism of PREX1 in gastric cancer.

METHODS

Bioinformatic analysis was performed in order to examine the expression of PREX1 in gastric cancer. The relationship between the survival rate of gastric cancer patients and PREX1 expression was assessed by Kaplan Meier portal. The Gene Set Enrichment Analysis and the correlation between PREX1 and transforming growth factor (TGF) β1 pathway-related mediators were evaluated by cBioPortal for Cancer Genomics. Western blotting and reverse transcriptase polymerase chain reaction assay were used to test the role of TGFβ1 on the expression of PREX1. Western blotting and dual-luciferase reporter system was used to evaluate the effect of PREX1 on the activation of TGFβ1 pathway. Wound healing and Transwell assay were used to assess the effect of PREX1 on the metastasis activity of gastric cancer cells.

RESULTS

PREX1 was overexpressed in the gastric tumors, and the expression levels were positively associated with the development of gastric cancer. Also, the high expression of PREX1 revealed poor prognosis, especially for those advanced and specific intestinal gastric cancer patients. PREX1 was closely involved in the positive regulation of cell adhesion and positively correlated with TGFβ1-related mediators. Furthermore, TGFβ1 could induce the expression of PREX1 at both the protein and mRNA level. Also, PREX1 could activate the TGFβ1 pathway. The induced PREX1 could increase the migration and invasion activity of gastric cancer cells.

CONCLUSION

PREX1 is overexpressed in gastric cancer, and the high level of PREX1 predicts poor prognosis. PREX1 is closely associated with TGFβ signaling and promotes the metastasis of gastric cancer cells.

Keywords: Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1, Gastric cancer, High expression, Poor prognosis, Metastasis, Transforming growth factor β1 pathway

Core tip: In this study, we fully identified the overexpression of phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 (PREX1) in gastric cancer and its positive correlation with the gastric cancer progression. High PREX1 expression predicts poor prognosis in the specific intestinal-type gastric cancer patients. PREX1 is closely involved with cell adhesion, and PREX1 has a positive feedback loop regulation with transforming growth factor β1 pathway to promote the metastasis of gastric cancer cells. PREX1 may be a novel target for the drug development of gastric cancer, and PREX1 acts as a predictor for prognosis of intestinal-specific gastric cancer.