Identification of RE1-Silencing Transcription Factor as a Promoter of Metastasis in Pancreatic Cancer

Frontiers in Oncology

Yang Gao¹  Haoyi Jin¹  Lingming Kong¹  Defeng Sun¹  Xiang Fei¹  Tianyu Wu¹  Xiaodong Tan²  Peng Liu² 

[1] Department of Surgery, Shengjing Hospital of China Medical University, Shenyang, China;Thyroid and Pancreatic Surgery Ward, Shengjing Hospital of China Medical University, Shenyang, China;

关键词: RE1-silencing transcription factor;    metastasis;    pancreatic cancer;    weighted gene co-expression network analysis;    prognosis;   

DOI  :  10.3389/fonc.2019.00291

来源: DOAJ

【 摘 要 】

Pancreatic cancer is characterized by its rapid progression and early metastasis. This requires further elucidation of the key promoters for its progression and metastasis. In this study, we identified REST as the hub gene of a gene module which is closely associated with cancer stage by weighted gene correlation network analysis. Validation with the TCGA database, western blot analysis of human pancreatic cancer cell lines (AsPC-1, Capan-2, SW-1990, and PANC-1) and immunohistochemical analysis of paraffin-embedded pancreatic cancer tissue sections showed that REST was enriched in tissue samples of advanced stage and metastatic phenotype cell lines. Survival analysis with the TCGA database and our own follow-up data suggested that patients with higher expression level of REST showed worse overall survival rate. In vitro functional experiments suggested that knockdown of REST suppressed proliferation, migration, invasion and epithelial-mesenchymal transition of AsPC-1 and PANC-1 cells. In vivo experiments (a subcutaneous BALB/c nude mouse model and a superior mesenteric vein injection BALB/c nude mouse model) suggested that knockdown of REST suppressed growth and metastasis of xenograft tumor. Finally, we investigated the underlying molecular mechanism of REST and identified REST as a potential downstream target of MAPK signaling pathway. In conclusion, our results of bioinformatic analysis, in vitro and in vivo functional analysis suggested that REST may serve as a promoter of metastasis in pancreatic cancer.

【 授权许可】

Unknown