Low tristetraprolin expression promotes cell proliferation and predicts poor patients outcome in pancreatic cancer.

// Zi-Ran Wei 1, * , Chao Liang 1, * , Dan Feng 2, * , Ya-Jun Cheng 1 , Wei-Min Wang 1 , De-Jun Yang 1 , Yue-Xiang Wang 3 , Qing-Ping Cai 1 1 Department of Gastro-Intestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China 2 Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, China 3 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 * These authors have contributed equally to this work Correspondence to: Qing-Ping Cai, email: wcwk2013@live.cn Yue-Xiang Wang, email: yxwang76@sibs.ac.cn Keywords: tristetraprolin, pancreatic cancer, IL-6, Pim-1, prognosis Received: July 14, 2015      Accepted: January 29, 2016      Published: February 15, 2016 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.