title: Epigenetic activation of SIN1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition.
abstract: Stress-activated protein kinase (SAPK) interacting protein 1 (SIN1) is an essential component of mTORC2. Previous studies have shown that SIN1 is a key regulator of Akt pathway which plays an important role in various pathological conditions including cancer. While its effects and mechanisms on the progression of NSCLC remain unknown. In this study, we report that SIN1 is able to promote the growth and migration of NSCLC cells both in vitro and in vivo. Overexpression of SIN1 promoted A549 and H1299 cells proliferation by both MTT and colony formation assays. Consistently, knockdown of SIN1 inhibited the proliferation of these cells. In transwell assay, overexpression of SIN1 increased the migration of A549 and H1299 cells, while SIN1 knockdown reduced their migration. In a tumor xenograft model, overexpression of SIN1 promoted tumor growth of A549 cells in vivo, while SIN1 knockdown suppresses the tumor growth. We also found a mechanistic link between SIN1 and H3K4me3, H3K4me3 is involved in SIN1 upregulation. Moreover, SIN1 can significantly promote the in vitro migration and invasion of NSCLC cells via induction epithelial mesenchymal transition (EMT) process, which subsequently leads to transcriptional downregulation of epithelial marker E-cadherin and upregulation of mesenchymal markers N-cadherin and Vimentin expression. Together, our results reveal that SIN1 plays an important role in NSCLC and SIN1 is a potential biomarker and a promising target in the treatment of NSCLC.
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, PR China.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, Jiangsu, 223002, PR China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Operation Anesthesiology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, PR China.
authors.forename: Yuemei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, PR China.
authors.forename: Bao
authors.initials: B
authors.lastname: Zang
authors.affiliation: Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, PR China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Hui
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, PR China.
authors.forename: Zhenbing
authors.initials: Z
authors.lastname: You
authors.affiliation: Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, PR China. Electronic address: wym7917@163.com.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014746:Vimentin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; C493277:MAPKAP1 protein, human; D014746:Vimentin
keywords: EMT; H3K4 trimethylation; Migration; NSCLC; SIN1