Sirtuin7 has an oncogenic potential via promoting the growth of cholangiocarcinoma cells

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Wenzhi Li, Zhe Sun, Chen Chen, Lin Wang, Zhimin Geng, Jie Tao
Accumulating evidence indicates that sirtuin7 (SIRT7) plays an oncogenic role in the main types of liver cancer, hepatocellular carcinoma (HCC). Nevertheless, the clinical significance of SIRT7 and its role in cholangiocarcinoma (CCA) is largely undiscovered. Here, we found that SIRT7 displayed higher expression in CCA tissues compared to intrahepatic normal bile duct and surrounding liver tissues based on The Cancer Genome Atlas (TCGA) data. Our data further confirmed that SIRT7 was overexpressed in CCA patient tissues and cell lines. Clinical analysis revealed that high SIRT7 expression was correlated with large tumor size and advanced tumor-node-metastasis (TNM) stage. Furthermore, SIRT7 overexpression independently predicted poor prognosis of CCA patients. Functionally, we demonstrated that SIRT7 knockdown suppressed proliferation and cell cycle progression of HUCCT1 cells in vitro and in vivo. SIRT7 restoration promoted the growth of QBC-939 cells. Mechanistically, SIRT7 reduced p21 expression and increased the levels of Cyclin D1 and cyclin dependent kinase 2 (CDK2) in CCA cells. Furthermore, microRNA-125b-5p (miR-125b-5p) was recognized as a direct negative regulator of SIRT7 and reduced SIRT7 abundance in CCA cells. Notably, miR-125b-5p restoration showed similar effects to SIRT7 knockdown on the growth of CCA cells. Taken together, we demonstrate for the first time that miR-125b-5p regulation of SIRT7 functions as an oncogene and a potential prognostic biomarker in CCA.

Graphical abstract

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