Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2023; 15(11): 1974-1987
Published online Nov 15, 2023. doi: 10.4251/wjgo.v15.i11.1974
Long non-coding RNA CDKN2B-AS1 promotes hepatocellular carcinoma progression via E2F transcription factor 1/G protein subunit alpha Z axis
Zhi-Gang Tao, Yu-Xiao Yuan, Guo-Wei Wang
Zhi-Gang Tao, Department of Radiology, Hangzhou Cancer Hospital, Hangzhou 310000, Zhejiang Province, China
Yu-Xiao Yuan, Guo-Wei Wang, Department of Radiology, Hangzhou Xixi Hospital, Hangzhou 310012, Zhejiang Province, China
Author contributions: Wang GW conceptualized the study; Tao ZG and Yuan YX performed the experiments, analyzed the data, and drafted the manuscript; and all authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by Ethics Committee of Hangzhou Cancer Hospital.
Informed consent statement: The surgical tissues and cells used in this study were not involved in the patients’ privacy information, so the informed consent was waived by the Ethics Committee of Hangzhou Cancer Hospital.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
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: Guo-Wei Wang, MD, MM, Attending Doctor, Department of Radiology, Hangzhou Xixi Hospital, No. 2 Hengbu Street, Xihu District, Hangzhou 310012, Zhejiang Province, China. wanguowei6987@126.com
Received: June 23, 2023
Peer-review started: June 23, 2023
First decision: August 30, 2023
Revised: September 12, 2023
Accepted: October 11, 2023
Article in press: October 11, 2023
Published online: November 15, 2023
Abstract
BACKGROUND

A series of long non-coding RNAs (lncRNAs) have been reported to play a crucial role in cancer biology. Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies. However, its role in hepatocellular carcinoma (HCC) has not been fully deciphered.

AIM

To decipher the role of CDKN2B-AS1 in the progression of HCC.

METHODS

CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction. The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method, EdU method, and flow cytometry, respectively. RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1 (E2F1). Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z (GNAZ). E2F1 and GNAZ were detected by western blot in HCC cells.

RESULTS

In HCC tissues, CDKN2B-AS1 was upregulated. Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells, and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis. CDKN2B-AS1 could interact with E2F1. Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region. Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.

CONCLUSION

CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression.

Keywords: Hepatocellular carcinoma, CDKN2B-AS1, E2F transcription factor 1, G protein subunit alpha Z, Proliferation

Core Tip: The high expression of long non-coding RNAs CDKN2B-AS1 in hepatocellular carcinoma (HCC) predicts poor prognosis of the patients, as it facilitates some malignant biological behaviors of HCC cells, including enhanced viability, proliferation, cell cycle progression, and anti-apoptosis ability. This study reveals one mechanism of CDKN2B-AS1 promoting HCC progression, which is the interaction between CDKN2B-AS1 and E2F transcription factor 1 in HCC cells to promote the expression of the oncogene G protein subunit alpha Z.