Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2019; 11(2): 91-101
Published online Feb 15, 2019. doi: 10.4251/wjgo.v11.i2.91
Novel long non-coding RNA LINC02532 promotes gastric cancer cell proliferation, migration, and invasion in vitro
Cheng Zhang, Ming-Hui Ma, Yu Liang, Kun-Zhe Wu, Dong-Qiu Dai
Cheng Zhang, Ming-Hui Ma, Yu Liang, Kun-Zhe Wu, Dong-Qiu Dai, Department of Gastroenterological Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
Author contributions: Dai DQ and Zhang C designed the study; Zhang C, Liang Y, Ma MH, and Wu KZ performed the experiments and data analysis; Zhang C wrote the paper.
Supported by National Natural Science Foundation of China, No. 30572162; and Natural Science Foundation of Liaoning Province, No. 201602817.
Institutional review board statement: The study was approved by the Clinical Research Ethics Committee of the Fourth Affiliated Hospital of China Medical University (approved number: EC-2016-KS-028) and was performed according to the standards of the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP).
Conflict-of-interest statement: None.
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: Dong-Qiu Dai, PhD, Professor, Department of Gastroenterological Surgery, The Fourth Affiliated Hospital of China Medical University, 4 Chongshan Road, Shenyang 110032, Liaoning Province, China. daidq63@163.com
Telephone: +86-24-62043110 Fax: +86-24-62043110
Received: November 12, 2018
Peer-review started: November 14, 2018
First decision: December 7, 2018
Revised: December 22, 2018
Accepted: January 8, 2019
Article in press: January 8, 2019
Published online: February 15, 2019
Abstract
BACKGROUND

Long non-coding RNAs (lncRNAs) are a kind of single-stranded RNA of more than 200 nucleotides in length and have no protein-coding function. Amounting studies have indicated that lncRNAs could play a vital role in the initiation and development of cancers, including gastric cancer (GC). Considering the crucial functions of lncRNAs, the identification and exploration of novel lncRNAs in GC is necessary.

AIM

To explore the role of novel lncRNA LINC02532 in GC.

METHODS

The upregulated LINC02532 was identified by processing the GC RNA-Seq data from The Cancer Genome Atlas. The qRT-PCR assay was performed to confirm the expression levels in GC cell lines and tissues. Cell proliferation, migration, and invasion were evaluated by the cell counting kit-8, colony formation, wound healing, and Transwell assays. The miRNAs downregulated in GC and sponged by LINC02532 were identified from and predicted by the data from the Firehose and RNA22 software programs, respectively. The miRNA downstream target genes were obtained from the TargetScan, miRDB, and DIANA online tools. Gene functional enrichment analysis was carried out using the Database for Annotation, Visualization, and Integrated Discovery software in the categories of cellular components, biological processes, molecular functions, and KEGG pathways.

RESULTS

The qRT-PCR assay demonstrated that the LINC02532 expression level was significantly upregulated in the GC cell lines and 52 paired tissues. Kaplan-Meier survival analysis based on The Cancer Genome Atlas data showed that patients with higher LINC02532 expression had poorer prognosis than those with lower LINC02532 expression. The correlation analysis between expression and clinicopathological features revealed that high expression of LINC02532 was associated with a high TNM stage (P = 0.008) and poor differentiation grade (P = 0.023). Functional experiments showed that LINC02532 promoted GC cell proliferation, migration, and invasion. According to the bioinformatics analysis, LINC02532 may act as a ceRNA by sponging downregulated miR-129-5p and miR-490-5p. Target genes of the two miRNAs were selected for further functional enrichment analysis. Importantly, KEGG pathway analysis showed that the genes were mainly involved in transcriptional misregulation in cancer, cell cycle, and TGF-beta, mTOR, and p53 signaling pathways.

CONCLUSION

The present study suggested that LINC02532 acted as an oncogene in GC and may be a promising target for therapy and prognosis management of GC.

Keywords: Gastric cancer, Long noncoding RNA, LINC02532, Prognosis, Bioinformatics

Core tip: Our study identified a novel long non-coding RNA LINC02532 and found that it was significantly overexpressed in gastric cancer (GC). Kaplan-Meier survival analysis showed that patients with higher LINC02532 expression had poorer prognosis than those with lower LINC02532 expression. The correlation analysis between expression and clinicopathological features revealed that the high expression of LINC02532 was associated with a high TNM stage and poor differentiation grade. Functional assays supported the finding that LINC02532 promoted GC cell proliferation, migration, and invasion. According to the bioinformatics analysis, LINC02532 may sponge downregulated miR-129-5p and miR-490-5p and participate in transcriptional misregulation in cancer, cell cycle, and TGF-beta, mTOR, and p53 signaling pathways.