Research Paper Volume 12, Issue 2 pp 1808—1827

ISG20 serves as a potential biomarker and drives tumor progression in clear cell renal cell carcinoma

Tianbo Xu 1, *, , Hailong Ruan 1, *, , Su Gao 2, , Jingchong Liu 1, , Yuenan Liu 1, , Zhengshuai Song 3, , Qi Cao 1, , Keshan Wang 1, , Lin Bao 1, , Di Liu 1, , Junwei Tong 1, , Jian Shi 1, , Huageng Liang 1, , Hongmei Yang 4, , Ke Chen 1, , Xiaoping Zhang 1, ,

  • 1 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 2 Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 3 Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 4 Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
* Equal contribution

received: August 29, 2019 ; accepted: January 2, 2020 ; published: January 30, 2020 ;

https://doi.org/10.18632/aging.102714
How to Cite

Copyright © 2020 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies and lacks reliable biomarkers for diagnosis and prognosis, which results in high incidence and mortality rates of ccRCC. In this study, ISG20, HJURP, and FOXM1 were identified as hub genes via weighted gene co-expression network analysis (WGCNA) and Cox regression analysis. Samples validation showed that only ISG20 was up-regulated in ccRCC. Therefore, ISG20 was selected for further study. High ISG20 expression was associated with poor overall survival and disease-free survival. Furthermore, the expression of ISG20 could effectively differentiate ccRCC from normal tissues and was positively correlated to clinical stages. Functional experiments proved that knockdown of ISG20 expression could obviously inhibit cell growth, migration, and invasion in ccRCC cells. To find the potential mechanisms of ISG20, gene set enrichment analysis (GSEA) was performed and revealed that high expression of ISG20 was significantly involved in metastasis and cell cycle pathways. In addition, we found that ISG20 could regulate the expression of MMP9 and CCND1. In conclusion, these findings suggested that ISG20 promoted cell proliferation and metastasis via regulating MMP9/CCND1 expression and might serve as a potential biomarker and therapeutic target in ccRCC.

Abbreviations

ccRCC: clear cell renal cell carcinoma; RCC: renal cell carcinoma; mRCC: metastatic RCC; WGCNA: weighted gene co-expression network analysis; ISGs: interferon stimulated genes; ISG20: interferon stimulated exonuclease Gene 20; HCC: hepatocellular carcinoma; TCGA: The Cancer Genome Atlas; DEGs: differentially expressed genes; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; TOM: topological overlap matrix; MEs: module eigengenes; OS: overall survival; DFS: disease-free survival; LASSO: least absolute shrinkage and selection operator; GEO: Gene Expression Omnibus; ROC: receiver operator characteristic; GSEA: gene set enrichment analysis; FDR: false discovery rate; HUST: Huazhong University of Science and Technology; ATCC: American Type Culture Collection; FBS: fetal bovine serum; qRT-PCR: quantitative real-time PCR; WB: western blotting; RIPA: radio-immunoprecipitation assay; IHC: immunohistochemical; CCK-8: cell counting kit-8; OD: optical density; MCT1: monocarboxylate transporter 1; MCT4: monocarboxylate transporter 4; CAMs: cell adhesion molecules; PPAR: peroxisome proliferators-activated receptors; IAV: influenza A virus; MMP: matrix metalloproteinase; MMP9: matrix metalloproteinase 9; CCND1: cyclin D1; HR: hazard ratio; CI: confidence interval; TNM: Tumor Node Metastasis; MM: module membership; GS: gene significance; CGA KIRC: The Cancer Genome Atlas Kidney Clear Cell Carcinoma.