Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2019; 25(39): 5973-5990
Published online Oct 21, 2019. doi: 10.3748/wjg.v25.i39.5973
Differentially expressed long noncoding RNAs and regulatory mechanism of LINC02407 in human gastric adenocarcinoma
Li-Li Zhou, Yan Jiao, Hong-Mei Chen, Li-Hua Kang, Qi Yang, Jing Li, Meng Guan, Ge Zhu, Fei-Qi Liu, Shuang Wang, Xue Bai, Yan-Qiu Song
Li-Li Zhou, Hong-Mei Chen, Li-Hua Kang, Meng Guan, Ge Zhu, Fei-Qi Liu, Shuang Wang, Xue Bai, Yan-Qiu Song, Cancer Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Yan Jiao, Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Qi Yang, Jing Li, Department of Radiology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Zhou LL, Jiao Y, and Chen HM designed this research and drafted the manuscript; Kang LH, Liu FQ, Wang S, and Bai X generated, collected, and analyzed the data; Yang Q and Li J interpreted the data; Guan M and Zhu G critically revised the manuscript; Song YQ conceived the study and revised the manuscript; all authors agree to be fully accountable for ensuring the integrity and accuracy of the work, and read and approved the final manuscript.
Supported by the Science and Technology Department of Jilin Province, No. 20160101028JC; and the Special Funds of Provincial Strategic Adjustment of Economic Structure to Guide in Jilin Province, No. 2014G074.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the First Hospital of Jilin University.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
Data sharing statement: The datasets supporting the conclusions of this article are included within the article.
ARRIVE guidelines statement: We 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: Yan-Qiu Song, MD, PhD, Academic Research, Director, Doctor, Full Professor, Professor, Teacher, Cancer Center, the First Hospital of Jilin University, Changchun 130021, Jilin Province, China. song_yq@jlu.edu.cn
Telephone: +86-431-88783829 Fax: +86-431-88786134
Received: May 27, 2019
Peer-review started: May 27, 2019
First decision: July 21, 2019
Revised: September 4, 2019
Accepted: September 13, 2019
Article in press: September 13, 2019
Published online: October 21, 2019
Processing time: 148 Days and 0.6 Hours
Abstract
BACKGROUND

Long noncoding RNAs (lncRNAs) have been identified to play important roles in the development and progression of various tumors, including gastric cancer (GC). However, the molecular role of lncRNAs in GC progression remains unclear.

AIM

To investigate the differential expression of lncRNAs in human GC and elucidate the function and regulatory mechanism of LINC02407.

METHODS

The Cancer Genome Atlas database was used to investigate the involvement of lncRNAs in GC. Quantitative real-time polymerase chain reaction was used to estimate the relative expression level of LINC02407 in GC tissues and cells. Functional experiments including CCK8 assay, apoptosis assay, wound healing assay, and transwell assay were used to investigate the effect of LINC02407 on GC cells. Some microRNAs were predicted and verified via bioinformatics analysis and the luciferase reporter system. Predictive analysis and Western blot assay were used to analyze the expression of related proteins.

RESULTS

Many differentially expressed lncRNAs were identified in GC, and some of them including LINC02407 can affect the survival. LINC02407 was upregulated in tumor tissues compared with adjacent tissues. HGC-27 cells showed the highest LINC02407 expression and HaCaT cells exhibited the lowest expression. Different experiment groups were constructed using LINC02407 overexpressing plasmids and related siRNAs. The results of functional experiments showed that LINC02407 can promote the proliferation, migration, and invasion of GC cells but inhibit apoptosis. Luciferase reporter assay showed that hsa-miR-6845-5p and hsa-miR-4455 was downstream regulated by LINC02407. Western blot analysis showed that adhesion G protein-coupled receptor D1 (ADGRD1) was regulated by the LINC02407-miR-6845-5p/miR-4455-ADGRD1 pathways.

CONCLUSION

LINC02407 plays a role in GC through the LINC02407-miR-6845-5p/miR-4455-ADGRD1 pathways, and thus, it may be an important oncogene and has potential value in GC diagnosis and treatment.

Keywords: Gastric cancer; Long noncoding RNAs; LINC02407; Adhesion G protein-coupled receptor D1; MicroRNA-6845-5p; MicroRNA-4455

Core tip: Many long noncoding RNAs were differentially expressed in gastric cancer (GC), some of which, including LINC02407, had significant impacts on the prognosis of patients. In vitro experiments showed that LINC02407 was significantly upregulated in GC cell lines and tissue samples, and could promote the proliferation and migration and inhibit apoptosis of GC cells. Mechanistic research found that LINC02407 can regulate the expression of adhesion G protein-coupled receptor D1 by targeting miR-6845-5p and miR-4455 and increased the malignancy of GC cells eventually. Our study provides evidence that LINC02407 may be an important oncogene and has potential value in GC diagnosis and treatment.