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Journal of Translational Medicine

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Open Access 01-12-2022 | Hepatocellular Carcinoma | Research

Identification of ZBTB9 as a potential therapeutic target against dysregulation of tumor cells proliferation and a novel biomarker in Liver Hepatocellular Carcinoma

Authors: Zhenshan Zhang, Leilei Wu, Juan Li, Jiayan Chen, Qi Yu, Hui Yao, Yaping Xu, Liang Liu

Published in: Journal of Translational Medicine | Issue 1/2022

Abstract

Background

Zinc finger and bric-a-brac/tramtrack/broad (ZBTB) domain-containing proteins have been reported to be associated with many tumors’ development. However, in tumor initiation and progression, the role of ZBTB9, one of the protein family, and its prognostic value were yet to be elucidated in Liver Hepatocellular Carcinoma (LIHC).

Methods

We used R software and online bioinformatics analysis tools such as GEPIA2, cBioPortal, TIMER2, Metascape, UALCAN, STRING, TISIDB, and COSMIC to investigate ZBTB9’s characteristics and function in LIHC, including abnormal expression, carcinogenic role, related signaling pathways and prognostic value. Furthermore, cell experiments (such as formation, wound healing, and transwell assays) and analyses based on clinical samples (such as immunohistochemistry (IHC) and promoter methylation analysis) were conducted to verify pivotal conclusions.

Results

ZBTB9 was overexpressed in LIHC samples compared to adjacent normal tissues. Through the analysis of genomic alteration and promoter hypomethylation, the clinical value and etiology of abnormal expression of ZBTB9 were preliminarily exlpored. Subsequent evidence showed that it could result in tumor progression and poor prognosis via activating cell cycle, DNA repair, MYC, and KRAS-associated signaling pathways as well as rendering immune dysregulation. After the knockdown of ZBTB9, evidently inhibited capacities of tumor cells proliferation and migration were observed. These results together indicated that ZBTB9 could be a promising prognostic biomarker and had the potential value to offer novel therapeutic targets for LIHC treatment.

Conclusions

ZBTB9 was identified as a novel biomarker to predict the prognosis and tumor progression in LIHC, and a promising therapeutic target to invert tumor development.

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Title: Identification of ZBTB9 as a potential therapeutic target against dysregulation of tumor cells proliferation and a novel biomarker in Liver Hepatocellular Carcinoma
Authors: Zhenshan Zhang
Leilei Wu
Juan Li
Jiayan Chen
Qi Yu
Hui Yao
Yaping Xu
Liang Liu
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Hepatocellular Carcinoma
Hepatocellular Carcinoma
Biomarkers
Published in: Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-022-03790-0

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