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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1409329
This article is part of the Research Topic Molecular Mechanisms and Targeted Therapies for Colorectal Cancer Vol II View all 4 articles

Identification and validation of metastasis-related gene ZG16 in the prognosis and progression in colorectal cancer

Provisionally accepted
Yulun Liu Yulun Liu Jie Yang Jie Yang Wei Han Wei Han Tingting Gu Tingting Gu Liqian Yao Liqian Yao Yongqiang Wang Yongqiang Wang *Hua Chen Hua Chen *
  • First People's Hospital of Kunshan, Kunshan, China

The final, formatted version of the article will be published soon.

    Background: Metastasis remains the leading cause of mortality among colorectal cancer (CRC) patients.Identification of new metastasis-related genes are critical to improve colorectal cancer prognosis.Methods: Data on mRNA expression in metastatic and primary CRC was obtained from the Gene Expression Omnibus (GEO) database, including GSE81986, GSE41568, GSE71222, GSE21510, and GSE14333. Additionally, data concerning mRNA expression in colon cancer (COAD) and adjacent normal tissues were acquired from The Cancer Genome Atlas (TCGA) database. Hub genes were identified by weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis. Moreover, we assessed the impact of hub gene expression on both overall survival (OS) and disease-free survival (DFS) in patients and identified ZG16 as a potential target. We generated CRC cell lines transfected with lentivirus OE-ZG16 to investigate proliferation, invasion, and migration in vitro. To further elucidate the involvement of ZG16, we utilized gene set enrichment analysis (GSEA) to identify enriched pathways, which were subsequently validated via Western blot analysis.Five datasets containing primary and metastatic CRC samples from GEO database and CRC samples from TCGA database were included in this study and 29 hub genes were identified by WGCNA and differentially expressed gene (DEG) analysis. Low expression of the hub genes (CLCA1 and ZG16) was associated with poor DFS and OS. We confirmed the low expression of ZG16 in CRC using external database and IHC analysis at both transcriptional and protein levels. In addition, the expression of ZG16 was notably elevated in NCM460 cells in comparison to CRC cell lines. The overexpression of ZG16 in CRC cells has been shown to inhibit the proliferation, invasion, and migration of CRC cells. Furthermore, the overexpression of ZG16 has been found to suppress the activation of the epithelial-mesenchymal transition (EMT) and Wnt/β-catenin signaling pathways in CRC.ZG16 may serve as a promising therapeutic target for metastatic CRC treatment.

    Keywords: colorectal cancer, ZG16, metastasis, EMT, Wnt/β-catenin

    Received: 29 Mar 2024; Accepted: 10 Jul 2024.

    Copyright: © 2024 Liu, Yang, Han, Gu, Yao, Wang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yongqiang Wang, First People's Hospital of Kunshan, Kunshan, China
    Hua Chen, First People's Hospital of Kunshan, Kunshan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.