<i>LITAF</i> is a potential tumor suppressor in pancreatic cancer

Abstract

// Yuan Zhou 1, 2, 4 , Jing Huang 1 , Xi Yu 1 , Xin Jiang 3 , Yaoyao Shi 3 , Yuanyuan Weng 3 , Yue Kuai 3 , Lizhen Lei 3 , Guoping Ren 4 , Xiaowen Feng 4 , Guoping Zhong 5 , Qingmeng Liu 6 , Hongyang Pan 7 , Xinxia Zhang 7 , Ren Zhou 3 and Caide Lu 1, 2 1 Department of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, China 2 Medical School of Ningbo University, Ningbo, China 3 Department of Pathology and Pathophysiology, Institute of Pathology and Forensic Medicine, Zhejiang University School of Medicine, Hangzhou, China 4 The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China 5 Division of Pathology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China 6 Division of Pathology, The Second People&rsquo;s Hospital, Shaoxing, China 7 Epitomics (Hangzhou) Inc., Hangzhou, Zhejiang, P.R. China Correspondence to: Caide Lu, email: lucaide@nbu.edu.cn Keywords: lipopolysaccharide-induced tumor necrosis factor-&alpha; factor (LITAF); pancreatic cancer; promoter methylation; tumor suppressor gene Received: April 20, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: November 15, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: December 14, 2017 ABSTRACT Early diagnosis of pancreatic cancer, one of the most deadly cancers with low survival rates, is difficult, and effective biomarkers are urgently needed. Lipopolysaccharide-induced tumor necrosis factor-&alpha; factor ( LITAF ) has been recently proposed as a potential tumor suppressor gene in several types of cancer. Here, we analyzed the biological function of LITAF in pancreatic cancer. The LITAF gene and protein levels were decreased in pancreatic tumor tissues compared with their paired adjacent non-cancerous tissues. In addition, patients with the lower LITAF protein expression had lower disease-free survival rates. The decreased LITAF expression correlated with LITAF promoter hypermethylation in pancreatic cancer cells and tissues. Moreover, promoter demethylation dose-dependently increased the LITAF transcription. Importantly, LITAF demethylation suppressed proliferation and cell cycle progression, and enhanced apoptosis of pancreatic cancer cells. Together, our results indicate that LITAF functions as a tumor suppressor gene in pancreatic cancer cells, and might serve as a novel biomarker for early diagnosis of pancreatic cancer.