OTUD4: A Potential Prognosis Biomarker for Multiple Human Cancers
Received 4 October 2019
Accepted for publication 14 February 2020
Published 28 February 2020 Volume 2020:12 Pages 1503—1512
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Antonella D'Anneo
Xiaohui Zhao,1,* Xiaobo Su,1,* Lu Cao,2 Tian Xie,3 Quan Chen,1 Jing Li,1 Rui Xu,4 Chao Jiang1,5
1GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, People’s Republic of China; 2Juancheng People’s Hospital, Heze City, Shandong Province 274600, People’s Republic of China; 3Obstetrics and Prenatal Diagnosis Center, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, People’s Republic of China; 4Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, People’s Republic of China; 5Department of Cancer Center, People’s Hospital of Baoan District, Shenzhen 518101, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiaohui Zhao
GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, People’s Republic of China
GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, Department of Cancer Center, People’s Hospital of Baoan District, Shenzhen 518101 People’s Republic of China
Background: Deubiquitinase OTU domain containing 4 (OTUD4) is initially identified as a K48-specific deubiquitinase and plays an important role in DNA damage repair signaling transduction. However, the expression level, prognostic role, biological function and mechanism of OTUD4 in multiple human cancers are unclear.
Methods: GEPIA online (http://gepia.cancer-pku.cn/; The Cancer Genome Atlas (TCGA) database) was used to analyze the mRNA expression of OTUD4 in multiple human cancers. Kaplan-Meier plotter (KM plotter) database and TCGA database were used to evaluate the prognostic value of OTUD4 expression in multiple human cancers. MTT, Transwell and 3D culture assays were used to detect the role of OTUD4 in breast, liver and lung cancer cells. The correlation between OTUD4 and apoptosis signaling pathway and AKT signaling pathway was analyzed by Gene set enrichment analysis (GSEA).
Results: OTUD4 mRNA expression is significantly downregulated in multiple human cancer tissues. Survival analysis establishes that the downregulation of OTUD4 predicts poor prognosis in many solid tumors, including breast invasive carcinoma (BRCA), esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and ovarian serous cystadenocarcinoma (OV). Furthermore, overexpression of OTUD4 could inhibit tumor cell proliferation, migration and invasion of breast, liver and lung cancer cells through inhibiting the AKT signaling pathway.
Conclusion: This study found that OTUD4 may be a potential predictive factor for several human cancers and a tumor suppressor for breast, liver and lung cancer. The overexpression of OTUD4 restrained proliferation, migration and invasion of human breast, liver and lung cancer cells through promoting cancer cells apoptosis and inhibiting AKT signaling pathway. Notably, our results indicated that OTUD4 could be a useful biomarker for the prognosis of human cancers and a potential molecular target for diagnosis and treatment of breast, liver and lung cancer.
Keywords: OTUD4, prognosis biomarker, proliferation, migration, invasion
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