Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2022; 28(20): 2184-2200
Published online May 28, 2022. doi: 10.3748/wjg.v28.i20.2184
Long noncoding RNA TNFRSF10A-AS1 promotes colorectal cancer through upregulation of HuR
Dan-Dan Wang, Dong-Lei Sun, Shao-Peng Yang, Jia Song, Meng-Yao Wu, Wei-Wei Niu, Mei Song, Xiao-Lan Zhang
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
ARTICLE HIGHLIGHTS
Research background

The critical importance of long noncoding RNAs (lncRNAs) to the onset and exacerbation of colorectal cancer (CRC) has been validated in an increasing number of studies. However, numerous lncRNAs associated with CRC remain unidentified and the detailed mechanisms remain poorly understood. TNFRSF10A-AS1 is a new lncRNA, the function in CRC and gastric cancer is inconsistent and the exact mechanism is unclear.

Research motivation

The present study will clarify the oncogenic pathogenesis of TNFRSF10A-AS1 in CRC progression, leading to new ideas for CRC therapy.

Research objectives

To detect TNFRSF10A-AS1 expression in CRC and investigate the functions and potential mechanisms of TNFRSF10A-AS1 in CRC onset and exacerbation.

Research methods

In this study, the authors detected TNFRSF10A-AS1 expression in CRC and clarified the relationship between TNFRSF10A-AS1 levels and clinicopathological features of CRC patients. Furthermore, a series of functional experiments both in vitro and in vivo were performed to explore the role of TNFRSF10A-AS1. The mechanism of TNFRSF10A-AS1 mainly focused on its role as a miRNA molecular sponge.

Research results

TNFRSF10A-AS1 expression was increased in CRC and positively associated with advanced tumor size and T grade of CRC patients. TNFRSF10A-AS1 enhanced the malignant phenotype of colon cancer cells by promoting CRC proliferation and metastasis. Mechanistically, TNFRSF10A-AS1 was more abundant in the cytoplasm and upregulated the downstream target, HuR, by sponging miR-3121-3p, ultimately promoting CRC progression.

Research conclusions

TNFRSF10A-AS1 upregulates HuR expression by sponging miR-3121-3p, ultimately promoting colorectal tumorigenesis and progression. Therefore, TNFRSF10A-AS1 and the TNFRSF10A-AS1/miR-3121-3p/HuR axis may play an important role in CRC onset and exacerbation.

Research perspectives

Targeting TNFRSF10A-AS1 and the TNFRSF10A-AS1/miR-3121-3p/HuR axis may have potential novel therapeutic implications for CRC.