Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2021; 27(17): 1993-2014
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.1993
Long non-coding RNA TP73-AS1 promotes pancreatic cancer growth and metastasis through miRNA-128-3p/GOLM1 axis
Bin Wang, Xing Sun, Ke-Jian Huang, Li-Sheng Zhou, Zheng-Jun Qiu
Bin Wang, Xing Sun, Ke-Jian Huang, Li-Sheng Zhou, Zheng-Jun Qiu, Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Author contributions: Qiu ZJ and Wang B conceived and supervised the study and wrote the manuscript; Wang B performed most of the experiments and data analyses; Sun X, Zhou LS, and Huang KJ performed Western blot experiments and data analysis; Zhou LS took part in the discussions; all the authors discussed the results, commented on the manuscript, and approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 81974372.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of Shanghai First People's Hospital Institutional Review Board (No. 2019KY065).
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 First People's Hospital (No. 2019 AW050).
Conflict-of-interest statement: The authors declare no conflicts of interest for this work.
Data sharing statement: The authors agree with the 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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zheng-Jun Qiu, MD, Chief Doctor, Director, Surgeon, Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China. qiuzjdoctor@sina.com
Received: December 14, 2020
Peer-review started: December 14, 2020
First decision: February 11, 2021
Revised: February 24, 2021
Accepted: March 24, 2021
Article in press: March 24, 2021
Published online: May 7, 2021
Processing time: 135 Days and 14.7 Hours
Abstract
BACKGROUND

Previous studies have suggested that long non-coding RNAs (lncRNA) TP73-AS1 is significantly upregulated in several cancers. However, the biological role and clinical significance of TP73-AS1 in pancreatic cancer (PC) remain unclear.

AIM

To investigate the role of TP73-AS1 in the growth and metastasis of PC.

METHODS

The expression of lncRNA TP73-AS1, miR-128-3p, and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p. The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation, migration, and invasion abilities were verified by Cell Counting Kit-8, wound-healing, and transwell assays, as well as flow cytometry and Western blot analysis. The interactions among TP73-AS1, miR-128-3p, and GOLM1 were explored by bioinformatics prediction, luciferase assay, and Western blot.

RESULTS

The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells. High TP73-AS1 expression was correlated with a poor prognosis. TP73-AS1 silencing inhibited PC cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. Mechanistically, TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p.

CONCLUSION

Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis, which might provide a potential treatment strategy for patients with PC.

Keywords: Pancreatic cancer; Long non-coding RNA; TP73-AS1; miR-128-3p; GOLM1

Core Tip: In this study, the expression level of TP73-AS1 in pancreatic cancer (PC) was measured and its clinical significance was assessed. In vitro and in vivo experiments were performed to determine the roles of TP73-AS1 in the progression and development of PC. Moreover, the underlying molecular mechanisms were also illustrated, which could provide a novel therapeutic target for patients with PC.