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

• Published in: Oncotarget Vol. 7; no. 14; pp. 17737 - 17750
• Main Authors: Wei, Zi-Ran, Liang, Chao, Feng, Dan, Cheng, Ya-Jun, Wang, Wei-Min, Yang, De-Jun, Wang, Yue-Xiang, Cai, Qing-Ping
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 05.04.2016
• Subjects: Animals; Cell Differentiation - physiology; Cell Line, Tumor; Cell Proliferation - physiology; Heterografts; Humans; Interleukin-6 - metabolism; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Prognosis; Research Paper; Survival Rate; Transfection; Tristetraprolin - biosynthesis; Tristetraprolin - metabolism; Pim-1; pancreatic cancer; prognosis; tristetraprolin; IL-6
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.7397

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.