Lin28B facilitates the progression and metastasis of pancreatic ductal adenocarcinoma

Abstract

// Yunchao Wang 1, 2, * , Jian Li 1, * , Shixiang Guo 1 , Yongsheng Ouyang 1 , Liangyu Yin 1 , Songsong Liu 1 , Zhiping Zhao 1 , Jiali Yang 1 , Wenjie Huang 3 , Huan Qin 1 , Xin Zhao 4 , Bing Ni 2 and Huaizhi Wang 1 1 Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China 2 Department of Pathophysiology and High Altitude Pathology, Third Military Medical University, Chongqing 400038, PR China 3 Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, PR China 4 Department of General Surgery, The First Affiliated Hospital, Soochow University, Jiangsu 215006, PR China * These authors have contributed equally to this work Correspondence to: Huaizhi Wang, email: whuaizhi@gmail.com Bing Ni, email: nibing@tmmu.edu.cn Xin Zhao, email: zhaox@suda.edu.cn Keywords: lin28B, pancreatic ductal adenocarcinoma, prognosis, therapeutic target, EMT Received: March 26, 2017     Accepted: June 25, 2017     Published: July 26, 2017 ABSTRACT Lin28B, a Lin28 homologue, represses the biogenesis of let-7 microRNAs (miRNAs), has a role in tumorigenesis, and is considered a potential therapeutic target for various human malignancies. However, the associations between Lin28B and the clinical features and outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we explored the clinical significance of Lin28B in PDAC and its association with metastasis by examining tissues from patients with PDAC and elucidated the molecular mechanisms using PDAC cell lines. In patients, high Lin28B expression was significantly correlated with high levels of lymphatic metastasis, distant metastasis and a poor prognosis. Furthermore, the multivariate analysis identified Lin28B expression as an independent prognostic factor in patients. In cell lines, stable silencing of Lin28B inhibited cell proliferation, cell cycle transition, migration and the epithelial-mesenchymal transition (EMT). It also increased the expression of the c-MYC, HMGA2 and KRAS genes, which are targeted by the cancer-suppressor miRNA let-7. Lin28B overexpression in the PDAC cell lines had the opposite effect. In human PDAC samples, high Lin28B expression was associated with decreased let-7 expression and increased c-MYC, HMGA2 and KRAS expression. Thus, Lin28B is a novel marker for predicting the prognosis of patients with PDAC and might be a potential therapeutic target for PDAC.