Next Article in Journal
A Splice Variant in SLC16A8 Gene Leads to Lactate Transport Deficit in Human iPS Cell-Derived Retinal Pigment Epithelial Cells
Next Article in Special Issue
Mapping the Metabolic Networks of Tumor Cells and Cancer-Associated Fibroblasts
Previous Article in Journal
Autophagy Involvement in the Postnatal Development of the Rat Retina
Open AccessArticle

SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma

1
Department of Emergency Medicine, Taipei Medical University—Shuang Ho Hospital, New Taipei City 235, Taiwan
2
Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei 110, Taiwan
3
Department of Emergency Medicine, School of Medicine, Taipei Medical University, Taipei 110, Taiwan
4
Department of Medical Research & Education, Taipei Medical University—Shuang Ho Hospital, New Taipei City 235, Taiwan
5
Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsinchu 300, Taiwan
6
Department of Pathology, Taipei Medical University—Shuang Ho Hospital, New Taipei City 235, Taiwan
7
Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
8
Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
*
Author to whom correspondence should be addressed.
Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei 110, Taiwan
Cells 2021, 10(1), 178; https://doi.org/10.3390/cells10010178
Received: 3 December 2020 / Revised: 14 January 2021 / Accepted: 14 January 2021 / Published: 17 January 2021
(This article belongs to the Special Issue Targeting Tumour Metabolism for Cancer Therapy)
Hepatocellular carcinoma (HCC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality globally. This is exacerbated by its highly aggressive phenotype, and limitation in early diagnosis and effective therapies. The SUMO-activating enzyme subunit 1 (SAE1) is a component of a heterodimeric small ubiquitin-related modifier that plays a vital role in SUMOylation, a post-translational modification involving in cellular events such as regulation of transcription, cell cycle and apoptosis. Reported overexpression of SAE1 in glioma in a stage-dependent manner suggests it has a probable role in cancer initiation and progression. In this study, hypothesizing that SAE1 is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of SAE1 in several cancer databases and to unravel the underlying molecular mechanism of SAE1-associated hepatocarcinogenesis. Here, we demonstrated that SAE1 is over-expressed in HCC samples compared to normal liver tissue, and this observed SAE1 overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of SAE1 in TCGA−LIHC patients (n = 421) showed an AUC of 0.925, indicating an excellent diagnostic value of SAE1 in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as PLK1, CCNB1, CDK4 and CDK1, while simultaneously inhibiting tumor suppressors including PDK4, KLF9, FOXO1 and ALDH2. Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort (n = 54) further validated the overexpression of SAE1 in cancerous liver tissues compared with ‘normal’ paracancerous tissue, and high SAE1 expression was strongly correlated with metastasis and disease progression. The oncogenic effect of upregulated SAE1 is associated with dysregulated cancer metabolic signaling. In conclusion, the present study demonstrates that SAE1 is a targetable cancer metabolic biomarker with high potential diagnostic and prognostic implications for patients with HCC. View Full-Text
Keywords: SAE1; hepatocellular carcinoma; SUMOylation; diagnosis; prognosis; metastasis SAE1; hepatocellular carcinoma; SUMOylation; diagnosis; prognosis; metastasis
Show Figures

Graphical abstract

MDPI and ACS Style

Ong, J.R.; Bamodu, O.A.; Khang, N.V.; Lin, Y.-K.; Yeh, C.-T.; Lee, W.-H.; Cherng, Y.-G. SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma. Cells 2021, 10, 178. https://doi.org/10.3390/cells10010178

AMA Style

Ong JR, Bamodu OA, Khang NV, Lin Y-K, Yeh C-T, Lee W-H, Cherng Y-G. SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma. Cells. 2021; 10(1):178. https://doi.org/10.3390/cells10010178

Chicago/Turabian Style

Ong, Jiann R.; Bamodu, Oluwaseun A.; Khang, Nguyen V.; Lin, Yen-Kuang; Yeh, Chi-Tai; Lee, Wei-Hwa; Cherng, Yih-Giun. 2021. "SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma" Cells 10, no. 1: 178. https://doi.org/10.3390/cells10010178

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop