Long non-coding RNA PVT1 activates hepatic stellate cells through competitively binding microRNA-152

// Jianjian Zheng 1,2 , Fujun Yu 3 , Peihong Dong 3 , Limei Wu 1 , Yuan Zhang 1 , Yanwei Hu 1 and Lei Zheng 1 1 Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China 2 Key Laboratory of Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China 3 Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China Correspondence to: Lei Zheng, email: // Keywords : plasmacytoma variant translocation 1 (PVT1); microRNA-152; DNA methylation; patched1 (PTCH1); Pathology Section Received : May 27, 2016 Accepted : August 25, 2016 Published : August 30, 2016 Abstract Epithelial-mesenchymal transition (EMT) process is considered as a key event in the activation of hepatic stellate cells (HSCs). Hedgehog (Hh) pathway is known to be required for EMT process. Long non-coding RNAs (lncRNAs) have been reported to be involved in a wide range of biological processes. Plasmacytoma variant translocation 1 (PVT1), a novel lncRNA, is often up-regulated in various human cancers. However, the role of PVT1 in liver fibrosis remains undefined. In this study, PVT1 was increased in fibrotic liver tissues and activated HSCs. Depletion of PVT1 attenuated collagen deposits in vivo . In vitro , PVT1 down-regulation inhibited HSC activation including the reduction of HSC proliferation, α-SMA and type I collagen. Further studies showed that PVT1 knockdown suppressed HSC activation was through inhibiting EMT process and Hh pathway. Patched1 (PTCH1), a negative regulator factor of Hh pathway, was enhanced by PVT1 knockdown. PTCH1 demethylation caused by miR-152 was responsible for the effects of PVT1 knockdown on PTCH1 expression. Notably, miR-152 inhibitor reversed the effects of PVT1 knockdown on HSC activation. Luciferase reporter assays and pull-down assays showed a direct interaction between miR-152 and PVT1. Collectively, we demonstrate that PVT1 epigenetically down-regulates PTCH1 expression via competitively binding miR-152, contributing to EMT process in liver fibrosis.