CEP131 indicates poor prognosis and promotes cell proliferation and migration in hepatocellular carcinoma |
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| Affiliation: | 1. Department of Emergency, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;2. Department of Pathology, Dongguan Third People''s Hospital, Dongguan, China;3. Department of Nursing, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;4. Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;5. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China;6. Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;1. UNESP – São Paulo State University, Botucatu Medical School, Department of Pathology, Botucatu, São Paulo State, Brazil;2. UNESP – São Paulo State University, Institute of Biosciences of Botucatu, Department of Morphology, Botucatu, São Paulo State, Brazil;3. UNESP – São Paulo State University, Institute of Biosciences of Botucatu, Department of Chemistry and Biochemistry, Botucatu, São Paulo State, Brazil;4. USP – University of São Paulo, School of Veterinary Medicine and Animal Science, Department of Pathology, São Paulo, São Paulo State, Brazil;1. Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, University of California, Los Angeles, Los Angeles, California, USA;2. Department of Molecular, Cell and Developmental Biology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA;1. Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada;2. Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada;3. Division of General Surgery, University Health Network, Toronto, Ontario, Canada;4. Department of Surgery, University of Toronto, Toronto, Ontario, Canada;1. Radiotherapy Department, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China;2. Department of Gastroenterology and Hepatology, Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Affiliated Hospital of University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China;3. Department of General Internal Medicine, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China;4. Department of Outpatient, Zaozhuang Traditional Chinese Medicine Hospital, No. 2666 Taihang Mountain Road, Xuecheng District, Zaozhuang, 277000, Shandong, China |
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| Abstract: | Centrosomal proteins have been implicated in the progression of human diseases. CEP131 plays important roles in centrosome duplication and genome stability, but its role in cancers remains largely unknown. Here, we showed that CEP131 expression was increased in hepatocellular carcinoma (HCC), compared to the paracarcinoma tissues, at both mRNA and protein levels. High CEP131 expression was closely associated with tumor size (P = 0.020), tumor capsule (P = 0.043), TNM stage (P = 0.007) and tumor differentiation (P = 0.019). Furthermore, patients with high expression of CEP131 were accompanied with worse overall and disease-free survivals in our and TCGA cohorts consisting of a total of 802 cases. The prognostic value of CEP131 was further confirmed by stratified survival analysis. Multivariate cox regression model indicated that CEP131 was an independent factor for overall survival (hazard ratio = 1.762, 95% confident interval: 1.443–2.151, P < 0.001). In vitro data demonstrated that nucleophosmin (NPM) physically bound to CEP131 and maintained its protein stability. Overexpression of CEP131 in HCC cell lines enhanced cell proliferation and migration, whereas the knockdown of CEP131 led to the opposite phenotypes. Further studies demonstrated that CEP131 exhibited oncogenic activity via activation of PI3K/AKT signaling pathway. Taken together, our findings suggest CEP131 serves as a potential prognostic biomarker in HCC, and functions as an oncogene in this deadly disease. |
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| Keywords: | CEP131 Proliferation Migration Prognosis Hepatocellular carcinoma |
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