Wang DD, Sun DL, Yang SP, Song J, Wu MY, Niu WW, Song M, Zhang XL. Long noncoding RNA TNFRSF10A-AS1 promotes colorectal cancer through upregulation of HuR. World J Gastroenterol 2022; 28(20): 2184-2200 [PMID: 35721888 DOI: 10.3748/wjg.v28.i20.2184]
Corresponding Author of This Article
Xiao-Lan Zhang, MD, PhD, Chief Physician, Department of Gastroenterology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei Province, China. xiaolanzh@126.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
Dan-Dan Wang, Dong-Lei Sun, Shao-Peng Yang, Jia Song, Meng-Yao Wu, Wei-Wei Niu, Mei Song, Xiao-Lan Zhang, Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Author contributions: Wang DD, Sun DL and Zhang XL conceived, designed the study; Wang DD, Sun DL, Yang SP and Song J performed most experiments, analyzed the data, wrote the manuscript and edited the paper; Sun DL and Zhang XL helped to supervise the study; Wu MY, Niu WW and Song M helped to perform the experiments and analyzed the data; Sun DL and Zhang XL helped to edit the paper.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Second Hospital of Hebei Medical University (No. 2021-R241).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee of the Second Hospital of Hebei Medical University (No. 2021-AE011).
Conflict-of-interest statement: There are no conflicts of interest to report.
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 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: Xiao-Lan Zhang, MD, PhD, Chief Physician, Department of Gastroenterology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei Province, China. xiaolanzh@126.com
Received: October 26, 2021 Peer-review started: October 26, 2021 First decision: December 27, 2021 Revised: January 10, 2022 Accepted: April 20, 2022 Article in press: April 20, 2022 Published online: May 28, 2022 Processing time: 213 Days and 4.3 Hours
Abstract
BACKGROUND
Recent studies have emphasized the emerging importance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). However, the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully elucidated.
AIM
To explore the functional role and underlying molecular mechanisms of lncRNA TNFRSF10A-AS1 in CRC.
METHODS
TNFRSF10A-AS1 expression was measured by quantitative real-time polymerase chain reaction in CRC, and the relationship between TNFRSF10A-AS1 levels and the clinicopathological features of CRC patients was analyzed. The effect of TNFRSF10A-AS1 expression on CRC proliferation and metastasis was examined in vitro and in vivo. Mechanistically, we investigated how TNFRSF10A-AS1 is involved in CRC as a competitive endogenous RNA.
RESULTS
TNFRSF10A-AS1 was expressed at a high level in CRC and the upregulation of TNFRSF10A-AS1 was associated with advanced T grade and tumor size in CRC patients. A functional investigation revealed that TNFRSF10A-AS1 enhanced the proliferation, migration ability and invasion ability of colon cancer cells in vitro and in vivo. A mechanistic analysis demonstrated that TNFRSF10A-AS1 acted as a miR-3121-3p molecular sponge to regulate HuR expression, ultimately promoting colorectal tumorigenesis and progression.
CONCLUSION
TNFRSF10A-AS1 exerts a tumor-promoting function through the miR-3121-3p/HuR axis in CRC, indicating that it may be a novel target for CRC therapy.
Core Tip: TNFRSF10A-AS1 was upregulated in colorectal cancer (CRC) tumor tissues and cell lines, and it was positively correlated with tumor grade and size in patients with CRC. In addition, TNFRSF10A-AS1 facilitated CRC growth and metastasis. Mechanistically, TNFRSF10A-AS1 was predominantly found in the cytoplasm of CRC cell lines and upregulated the level of the downstream target, HuR, by sponging miR-3121-3p, thereby further promoting colorectal tumorigenesis and progression.
