title: Low tristetraprolin expression promotes cell proliferation and predicts poor patients outcome in pancreatic cancer.
abstract: Tristetraprolin (also known as TTP, TIS11, ZFP36, and Nup475) is a well-characterized tumor suppressor that is down-regulated in several tumor types. In the current study, we found that TTP expression was markedly reduced in pancreatic cancer samples as compared to matched normal tissues. Low TTP level was associated with age (P=0.037), tumor size (P=0.008), tumor differentiation (P=0.004), postoperative T stage (pT stage, P<0.001), postoperative N stage (pN stage, P=0.008) and TNM stage (P<0.001). Moreover, low TTP expression predicted reduced survival rates and poor patient outcome. We also found that TTP impairs pancreatic cancer cell proliferation both in vivo and in vitro. Fluorescence Activated Cell Sorting (FACS) assay showed that TTP over-expression both increases apoptosis and decreases proliferation in pancreatic cancer cells. RNA-sequencing analysis showed that TTP over-expression downregulates several tumor-related factors, including Pim-1 and IL-6. Our findings indicate that TTP could serve as a potential prognostic indicator in pancreatic cancer.
authors.affiliation: Department of Gastro-Intestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zi-Ran
authors.initials: ZR
authors.lastname: Wei
authors.affiliation: Department of Gastro-Intestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Gastro-Intestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: Department of Gastro-Intestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Wang
authors.affiliation: Department of Gastro-Intestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: De-Jun
authors.initials: DJ
authors.lastname: Yang
authors.affiliation: SIBS (Institute of Health Sciences)-Changzheng Hospital Joint Center for Translational Medicine, Institute of Health Sciences, Shanghai Changzheng Hospital, Institutes for Translational Medicine (CAS-SMMU), Key Laboratory of Stem Cell Biology, Institute of Health Sciences, SIBS, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai, China.
authors.forename: Yue-Xiang
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of Gastro-Intestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Cai
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D064593:Heterografts; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D014162:Transfection; D051816:Tristetraprolin / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D051816:Tristetraprolin
keywords: IL-6; Pim-1; pancreatic cancer; prognosis; tristetraprolin