Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2019; 25(44): 6508-6526
Published online Nov 28, 2019. doi: 10.3748/wjg.v25.i44.6508
Long noncoding RNA NALT1-induced gastric cancer invasion and metastasis via NOTCH signaling pathway
Hai-Yan Piao, Shuai Guo, Yue Wang, Jun Zhang
Hai-Yan Piao, Medical Oncology Department of Gastrointestinal Cancer, Liaoning Province Cancer Hospital & Institute (Cancer Hospital of China Medical University), Shenyang 110042, Liaoning Province, China
Shuai Guo, Yue Wang, Jun Zhang, Gastric Cancer Department, Liaoning Province Cancer Hospital & Institute (Cancer Hospital of China Medical University), Shenyang 110042, Liaoning Province, China
Author contributions: Zhang J designed the research; Piao HY performed the majority of experiments, analyzed the data, and drafted the manuscript; Guo S conducted the molecular biology assays and assisted in writing the manuscript; Wang Y collected and analyzed the data.
Supported by Liaoning S&T Project, No. 20180550971 and No. 20170520447; and CSCO-MERCK SERNO oncology research fund, No. Y-MX2016-031.
Institutional review board statement: The study was reviewed and approved by the Faculty of Science Ethics Committee at Liaoning Cancer Hospital & Institute (Cancer Hospital of China Medical University) (20150308-2).
Informed consent statement: All study participants provided informed written consent prior to their treatments and study enrollment.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Jun Zhang, MD, Doctor, Gastric Cancer Department, LiaoNing Cancer Hospital & Institute (Cancer Hospital of China Medical University) No. 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China. zhangjun@cancerhosp-ln-cmu.com
Telephone: +86-24-31916823 Fax: +86-24-2431-5679
Received: August 30, 2019
Peer-review started: August 30, 2019
First decision: October 14, 2019
Revised: October 30, 2019
Accepted: November 13, 2019
Article in press: November 13, 2019
Published online: November 28, 2019
Processing time: 90 Days and 3.1 Hours
ARTICLE HIGHLIGHTS
Research background

Gastric cancer (GC) is the most common and aggressive tumor of the digestive system and poses a serious threat to human health. Long noncoding RNAs (lncRNAs) are aberrant and play critical roles in GC. Since genes do not work alone, our aim was to elucidate the potential relationship between mRNA and noncoding RNA in this study.

Research motivation

Searching for coexpressed lncRNA clusters may help to elucidate the mechanism of tumor development and predict the prognosis of GC.

Research objectives

To explore the prognostic value of NOTCH1 associated with lncRNA in T cell acute lymphoblastic leukemia 1 (NALT1) in GC and the mechanism of its involvement in gastric cancer invasion and metastasis.

Research methods

Based on the TCGA database, we obtained differentially expressed lncRNAs. The significance module was studied by weighted gene coexpression network analysis. The function of NALT1 was assessed by reverse transcription polymerase chain reaction, western blotting, scrape motility assay, and Transwell migration assay.

Research results

Fifteen coexpression modules were constructed based on 3339 differentially expressed lncRNAs and weighted gene coexpression network analysis. The blue module was correlated with tumor grade and survival, and the hub-lncRNA of blue NALT1 was an independent risk factor for GC prognosis. Through cis regulation, NALT1 affected the expression of the NOTCH signaling pathway and was related to GC invasion and metastasis.

Research conclusions

NALT1 was overexpressed in GC and was an independent risk factor for GC prognosis. It affected invasion and metastasis of GC by regulating NOTCH1 and NOTCH signaling pathway.

Research perspectives

In future studies, we will verify the results of this study through in vivo experiments. The specific binding sites of NALT1 and NOTCH1 will be studied by chromatin immunoprecipitation and pull-down assays.