Qin YC, Yan X, Yuan XL, Yu WW, Qu FJ. Osteopontin promotes gastric cancer progression via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. World J Gastrointest Oncol 2023; 15(9): 1544-1555 [PMID: 37746644 DOI: 10.4251/wjgo.v15.i9.1544]
Corresponding Author of This Article
Fan-Jie Qu, MD, Professor, Department of Oncology, Affiliated Dalian Third People’s Hospital of Dalian Medical University, No. 40 Qianshan Road, Dalian 116033, Liaoning Province, China. wyb960419@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
Yue-Chao Qin, Xin Yan, Wei-Wei Yu, Fan-Jie Qu, Department of Oncology, Affiliated Dalian Third People’s Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China
Yue-Chao Qin, Xiao-Lin Yuan, Research Center, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning Province, China
Author contributions: Qu FJ and Yuan XL designed this study; Qin YC and Yan X directed the experiment technology; Qin YC and Yu WW performed the experiments; Qin YC prepared the figures and drafted the manuscript; Qu FJ helped to revising of manuscript; All authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Affiliated Dalian Third People’s Hospital of Dalian Medical University.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fan-Jie Qu, MD, Professor, Department of Oncology, Affiliated Dalian Third People’s Hospital of Dalian Medical University, No. 40 Qianshan Road, Dalian 116033, Liaoning Province, China. wyb960419@163.com
Received: April 11, 2023 Peer-review started: April 11, 2023 First decision: July 9, 2023 Revised: July 14, 2023 Accepted: July 28, 2023 Article in press: July 28, 2023 Published online: September 15, 2023 Processing time: 154 Days and 19.9 Hours
ARTICLE HIGHLIGHTS
Research background
Gastric cancer (GC) is one of the most common malignant tumors. Osteopontin (OPN) is thought to be closely related to the occurrence, metastasis and prognosis of many types of tumors.
Research motivation
To search for a potential prognostic biomarker for GC as well as a potential therapeutic target.
Research objectives
The purpose of this study was to investigate the effects of OPN on the proliferation, invasion and migration of GC cells and its possible mechanism.
Research methods
The mRNA and protein expression of OPN in the GC cells were analyzed by real-time quantitative-reverse transcription and western blotting, and observe the effect of varying degree expression OPN on the proliferation and other behaviors of GC. Next, the effects of OPN knockdown on GC cells migration and invasion were examined. The short hairpin RNA (shRNA) and negative control shRNA targeting OPN-shRNA were transfected into the cells according to the manufacturer’s instructions. Non transfected cells were classified as control in the identical transfecting process. 24 h after RNA transfection cell proliferation activity was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide assay, and cell invasiveness and migration were detected by Trans well assay. Meanwhile, the expression of protein kinase B (AKT), matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF) in the human GC cell lines was detected by reverse transcription polymerase chain reaction and western blotting.
Research results
The results of this study revealed that OPN mRNA and protein expression levels were highly expressed in SGC-7901 cells. OPN knockdown by specific shRNA noticeably reduced the capabilities of proliferation, invasion and migration of SGC-7901 cells. Moreover, in the experiments of investigating the underlying mechanism, results showed that OPN knockdown could down- regulated the expression of MMP-2 and VEGF, it also decreased the phosphorylation of AKT. Meanwhile, the protein expression levels of MMP-2, VEGF and phosphorylated AKT was noticeable lower than that in control group in the GC cells after they were added to phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002).
Research conclusions
These results suggested that OPN though PI3K/AKT/mammalian target of rapamycin signal pathway to up-regulate MMP-2 and VEGF expression, which contribute SGC-7901 cells to proliferation, invasion and migration. Thus, our results demonstrate that OPN may serve as a novel prognostic biomarkers as well as a potential therapeutic targets for GC.
Research perspectives
The effects of OPN on proliferation, invasion and migration of GC cells were confirmed by preliminary evidence, which may be used as a prognostic biomarker and potential therapeutic target in the future.
