Chen C, Lin HG, Yao Z, Jiang YL, Yu HJ, Fang J, Li WN. Transcription factor glucocorticoid modulatory element-binding protein 1 promotes hepatocellular carcinoma progression by activating Yes-associate protein 1. World J Gastrointest Oncol 2023; 15(6): 988-1004 [PMID: 37389116 DOI: 10.4251/wjgo.v15.i6.988]
Corresponding Author of This Article
Cheng Chen, MM, Attending Doctor, Department of Medical Oncology, Zhejiang Xiaoshan Hospital, No. 728 Yucai North Road, Xiaoshan District, Hangzhou 311202, Zhejiang Province, China. chencheng858@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/
Cheng Chen, Yi-Ling Jiang, Hong-Jin Yu, Jing Fang, Wei-Na Li, Department of Medical Oncology, Zhejiang Xiaoshan Hospital, Hangzhou 311202, Zhejiang Province, China
Hai-Guan Lin, Department of General Surgery, People’s Liberation Army Strategic Support Force Characteristic Medical Center, Beijing 100101, China
Zheng Yao, Department of Radiation Oncology, Cancer Hospital of The University of Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China
Author contributions: Chen C and Lin HG contributed equally to this work; Chen C, Lin HG and Yao Z designed the research; Lin HG, Yao Z, Jiang YL and Yu HJ contributed to methodological establishment and completion of experiments; Lin HG, Yao Z, Jiang YL, Yu HJ, Fang J and Li WN analyzed and interpreted the data; Chen C and Lin HG drafted the manuscript; Chen C and Fang J and Li WN critically revised the manuscript for important intellectual content.
Institutional review board statement: The study was reviewed and approved by Ethics Committee of Zhejiang Xiaoshan Hopital.
Institutional animal care and use committee statement: The experimental protocol was approved by the Animal Care and Use Committee of Zhejiang Xiaoshan Hopital.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Cheng Chen, MM, Attending Doctor, Department of Medical Oncology, Zhejiang Xiaoshan Hospital, No. 728 Yucai North Road, Xiaoshan District, Hangzhou 311202, Zhejiang Province, China. chencheng858@126.com
Received: January 17, 2023 Peer-review started: January 17, 2023 First decision: February 28, 2023 Revised: March 18, 2023 Accepted: April 12, 2023 Article in press: April 12, 2023 Published online: June 15, 2023 Processing time: 148 Days and 18.2 Hours
Abstract
BACKGROUND
Glucocorticoid modulatory element-binding protein 1 (GMEB1), which has been identified as a transcription factor, is a protein widely expressed in various tissues. Reportedly, the dysregulation of GMEB1 is linked to the genesis and development of multiple cancers.
AIM
To explore GMEB1’s biological functions in hepatocellular carcinoma (HCC) and figuring out the molecular mechanism.
METHODS
GMEB1 expression in HCC tissues was analyzed employing the StarBase database. Immunohistochemical staining, Western blotting and quantitative real-time PCR were conducted to examine GMEB1 and Yes-associate protein 1 (YAP1) expression in HCC cells and tissues. Cell counting kit-8 assay, Transwell assay and flow cytometry were utilized to examine HCC cell proliferation, migration, invasion and apoptosis, respectively. The JASPAR database was employed for predicting the binding site of GMEB1 with YAP1 promoter. Dual-luciferase reporter gene assay and chromatin immunoprecipitation-qPCR were conducted to verify the binding relationship of GMEB1 with YAP1 promoter region.
RESULTS
GMEB1 was up-regulated in HCC cells and tissues, and GMEB1 expression was correlated to the tumor size and TNM stage of HCC patients. GMEB1 overexpression facilitated HCC cell multiplication, migration, and invasion, and suppressed the apoptosis, whereas GMEB1 knockdown had the opposite effects. GMEB1 bound to YAP1 promoter region and positively regulated YAP1 expression in HCC cells.
CONCLUSION
GMEB1 facilitates HCC malignant proliferation and metastasis by promoting the transcription of the YAP1 promoter region.
Core Tip: Glucocorticoid modulatory element-binding protein 1 (GMEB1) was highly expressed in hepatocellular carcinoma (HCC) tissues. Functionally, GMEB1 modulates the malignant biological behaviors of HCC cells. Mechanistically, GMEB1 promotes the expression of Yes-associate protein 1 at transcriptional level. In short, the present study suggested that for HCC, GMEB1 might be a diagnostic biomarker and treatment target.
