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
Abstract
BACKGROUND

Long noncoding RNAs (lncRNAs) are aberrant and play critical roles in gastric cancer (GC) progression and metastasis. Searching for coexpressed lncRNA clusters or representative biomarkers related to malignant phenotypes of GC may help to elucidate the mechanism of tumor development and predict the prognosis of GC.

AIM

To investigate 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 GC invasion and metastasis.

METHODS

RNA sequencing and corresponding clinical data were downloaded from The Cancer Genome Atlas database. The significance module was studied by weighted gene coexpression network analysis. A total of 336 clinical samples were included in the study. Gene silencing, reverse transcription polymerase chain reaction, western blotting, scrape motility assay, and Transwell migration assay were used to assess the function of hub-lncRNAs.

RESULTS

At the transcriptome level, 3339 differentially expressed lncRNAs were obtained. weighted gene coexpression network analysis was used to obtain 15 lncRNA clusters and observe their coexpression. Pearson’s correlation showed that blue module was correlated with tumor grade and survival. NALT1 was the hub-lncRNA of blue module and was an independent risk factor for GC prognosis. NALT1 was overexpressed in GC and its expression was closely related to invasion and metastasis. The mechanism may involve NALT1 regulation of NOTCH1, which is associated with lncRNA in T cell acute lymphoblastic leukemia, through cis regulation, thereby affecting the expression of the NOTCH signaling pathway.

CONCLUSION

NALT1 is overexpressed and promotes invasion and metastasis of GC. The mechanism may be related to regulation of NOTCH1 by NALT1 and its effect on NOTCH signaling pathway expression.

Keywords: Gastric cancer; Weighted gene coexpression network analysis; NALT1; NOTCH1; Cancer survival

Core tip: Analysis of the Cancer Genome Atlas and clinical data revealed that the long noncoding RNA (lncRNA) NOTCH1 associated with lncRNA in T cell acute lymphoblastic leukemia 1 (NALT1) was associated with poor prognosis of gastric cancer (GC). We investigated the possible mechanism of this association. We downloaded the Cancer Genome Atlas-Stomach Adenocarcinoma RNA-seq data and identified the differentially expressed lncRNAs. Weighted gene coexpression network analysis was used to clarify the connection between modules and clinical information. We then chose lncRNA NALT1 as the hub-lncRNA of blue-module. NALT1 was overexpressed in GC and promoted invasion and metastasis of GC. The over-expression of NALT1 was linked to poor prognosis in GC. The mechanism may be related to the regulation of NOTCH1 by NALT1 and its effect on the expression of NOTCH signaling pathway.