SIRT1 facilitates hepatocellular carcinoma metastasis by promoting PGC-1α-mediated mitochondrial biogenesis
| Autor: | Jing Li, Shangcheng Xu, Ye-Wang Tian, Min Feng, Xiaobing Huang, Nan You, Lu Zheng, Hongzhi Zhao, Ping Liang, Guohua Zuo, Zhou Zhou, Ping Deng, Yuming Li, Zhengping Yu, Huifeng Pi, Hongyan Li, Ke-qiang Han, Xiaoya Wang, Min Li |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pathology mitochondrial biogenesis endocrine system diseases PGC-1α Kaplan-Meier Estimate environment and public health Metastasis Mice Sirtuin 1 Gene knockdown Organelle Biogenesis biology Liver Neoplasms hepatocellular carcinoma Middle Aged Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Oncology Hepatocellular carcinoma Heterografts Female biological phenomena cell phenomena and immunity hormones hormone substitutes and hormone antagonists Research Paper Adult medicine.medical_specialty Carcinoma Hepatocellular Mice Nude Disease-Free Survival 03 medical and health sciences SIRT1 Downregulation and upregulation medicine Animals Humans metastasis Neoplasm Invasiveness Aged business.industry medicine.disease enzymes and coenzymes (carbohydrates) 030104 developmental biology Mitochondrial biogenesis biology.protein Cancer research Ectopic expression Organelle biogenesis business |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.8711 |
| Popis: | // Yuming Li 1, * , Shangcheng Xu 2, * , Jing Li 1 , Lu Zheng 1 , Min Feng 2 , Xiaoya Wang 3 , Keqiang Han 1 , Huifeng Pi 2 , Min Li 2 , Xiaobing Huang 1 , Nan You 1 , Yewang Tian 1 , Guohua Zuo 1 , Hongyan Li 1 , Hongzhi Zhao 1 , Ping Deng 2 , Zhengping Yu 2 , Zhou Zhou 2 , Ping Liang 1 1 Department of Hepatobiliary Surgery, Second Affiliated Hospital of Third Military Medical University, Chongqing 400037, China 2 Department of Occupational Health, Third Military Medical University, Chongqing 400038, China 3 Department of Military Nursing, School of Nursing, Third Military Medical University, Chongqing 400038, China * These authors contributed equally to this work Correspondence to: Ping Liang, e-mail: lpxqyy@163.com Zhou Zhou, e-mail: lunazhou00@163.com Keywords: SIRT1, PGC-1α, mitochondrial biogenesis, metastasis, hepatocellular carcinoma Received: November 25, 2015 Accepted: March 28, 2016 Published: April 12, 2016 ABSTRACT SIRT1 is a multifaceted NAD + -dependent protein deacetylase known to act as a tumor promoter or suppressor in different cancers. Here, we describe a novel mechanism of SIRT1-induced hepatocellular carcinoma (HCC) metastasis. SIRT1 overexpression was frequently detected in human HCC specimens and was associated with microvascular invasion ( P = 0.0039), advanced tumor node metastasis (TNM) stages ( P = 0.0016), HCC recurrence ( P = 0.021) and poor outcomes ( P = 0.039). Lentivirus-mediated knockdown of SIRT1 in MHCC97H cells reduced invasion and metastasis in vitro and in vivo . SIRT1 depletion attenuated mitochondrial biogenesis and adenosine triphosphate (ATP) production but did not affect epithelial-mesenchymal transition. Elevated SIRT1 expression strongly correlated with the upregulation of PGC-1α in HCC specimens, and ectopic expression of SIRT1 increased PGC-1α levels. In cell assays and an orthotopic transplantation model, PGC-1α overexpression reversed the inhibitory effects of SIRT1 depletion on invasion and metastasis by enhancing mitochondrial biogenesis. These findings reveal the involvement of SIRT1 in HCC metastasis and provide a rationale for exploring therapeutic targets against the SIRT1/PGC-1α axis. |
| Databáze: | OpenAIRE |
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