Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2022; 28(35): 5141-5153
Published online Sep 21, 2022. doi: 10.3748/wjg.v28.i35.5141
Long noncoding RNA negative regulator of antiviral response contributes to pancreatic ductal adenocarcinoma progression via targeting miR-299-3p
Hai-Quan Wang, Chun-Hua Qian, Zeng-Ya Guo, Pei-Ming Li, Zheng-Jun Qiu
Hai-Quan Wang, Zheng-Jun Qiu, Department of General Surgery, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, China
Hai-Quan Wang, Zeng-Ya Guo, Pei-Ming Li, Zheng-Jun Qiu, Department of General Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Chun-Hua Qian, Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, Shanghai 200072, China
Author contributions: Qiu ZJ and Wang HQ designed the experiments and revised the manuscript; Qian CH and Wang HQ performed most of the experiments; Li PM and Guo ZY analyzed the data; Wang HQ and Guo ZY wrote the manuscript; all authors discussed the results and reviewed the manuscript.
Supported by the National Natural Science Foundation of China, No. 81974372.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Animal Ethics Committee of Shanghai General Hospital, No. SHDSYY-2020-T1663.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: The authors are amenable to data sharing.
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 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: Zheng-Jun Qiu, MD, Chief Doctor, Director, Surgeon, Department of General Surgery, Shanghai General Hospital of Nanjing Medical University, No. 100 Haining Road, Shanghai 200080, China. qiuzjdoctor@sina.com
Received: November 9, 2021
Peer-review started: November 9, 2021
First decision: April 16, 2022
Revised: April 28, 2022
Accepted: September 1, 2022
Article in press: September 1, 2022
Published online: September 21, 2022
Abstract
BACKGROUND

Pancreatic ductal cancer (PDAC) has high malignancy and poor prognosis. Long noncoding RNAs (lncRNAs) are associated with high levels of malignancy, including PDAC. However, the biological and clinical significance of negative regulator of antiviral response (NRAV) in PDAC is unclear.

AIM

To study the regulatory role of lncRNA NRAV in PDAC.

METHODS

GEPIA analyzed lncRNA NRAV and miRNA (miR-299-3p) expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time. The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis, Cell Counting Kit-8 and Transwell analysis. The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics, RNA immunoassay, and fluorescence enzyme analysis. In vivo experiments included transplantation of simulated tumor cells under naked mice.

RESULTS

The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients. Functionally, overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells, while knockdown of NRAV reversed these effects. Finally, NRAV was performed as a molecular sponge of miR-299-3p. Moreover, overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.

CONCLUSION

NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.

Keywords: Long noncoding RNA, Negative regulator of antiviral response, miR-299-3p, Proliferation, Migration, Invasion, Pancreatic cancer

Core Tip: In the present research, the expression level of long noncoding RNA negative regulator of antiviral response (NRAV) in pancreatic ductal adenocarcinoma (PDAC) was detected, and the clinicopathological relationship between NRAV and PDAC was demonstrated. Moreover, cell and animal tests were conducted to assess the concrete roles of NRAV in the progression of PDAC. Finally, the existence of potential specific molecular mechanisms that can provide new ideas for finding new molecular markers for the diagnosis and treatment of PDAC is demonstrated.