title: SIRT 1 Overexpression is Associated with Metastasis of Pancreatic Ductal Adenocarcinoma (PDAC) and Promotes Migration and Growth of PDAC Cells.
abstract: BACKGROUND SIRT 1, as a class III histone deacetylase (HDAC), is implicated in the initiation and progression of malignancies. However, the association of SIRT 1 with tumorigenesis or progression of pancreatic ductal adenocarcinoma (PDAC) is not clear. MATERIAL AND METHODS In our study we investigated SIRT 1 expression in PDAC samples and evaluated the association of SIRT 1 level with the clinical and pathological characteristics of PDAC patients. We investigated the role of SIRT 1 in the migration and growth of PDAC PANC-1 or BxPC-3 cells using gain-of-function and loss-of-function approach. RESULTS We demonstrated that SIRT 1 mRNA level was significantly promoted in intra-tumor tissues compared to peri-tumor tissues of PDAC; and SIRT 1 overexpression was markedly associated with distant or lymph node (LN) metastasis of these PDAC tissues. Moreover, the in vitro wound healing assay demonstrated that SIRT 1 overexpression with lentivirus vector markedly promoted the migration of PANC-1 or BxPC-3 cells, whereas SIRT 1 knockdown using SIRT 1 specific siRNA transfection significantly inhibited the migration of PDAC cells. The colony forming assay confirmed SIRT 1 promotion of the growth of PANC-1 or BxPC-3 cells. CONCLUSIONS In summary, SIRT 1 overexpression is significantly associated with metastasis of PDAC, and overexpressed SIRT 1 plays an important role in pancreatic cancer cell migration and growth. Our data warrants further studies on SIRT 1 as a novel chemotherapeutic target in PDAC.
authors.affiliation: Institute of Ultrasound Imaging, Second Clinical College of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Siqin
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Ultrasound Medicine, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, China (mainland).
authors.forename: Hua
authors.initials: H
authors.lastname: Hong
authors.affiliation: Second Department of Traumatology, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China (mainland).
authors.forename: Huicheng
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Ultrasound Medicine, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, China (mainland).
authors.forename: Guozhu
authors.initials: G
authors.lastname: Wu
authors.affiliation: Institute of Ultrasound Imaging, Second Clinical College of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C447939:SIRT1 protein, human; D056564:Sirtuin 1