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Long non-coding RNA PVT1 activates hepatic stellate cells through competitively
binding microRNA-152
#MMPMID27588491
Zheng J
; Yu F
; Dong P
; Wu L
; Zhang Y
; Hu Y
; Zheng L
Oncotarget
2016[Sep]; 7
(39
): 62886-62897
PMID27588491
show ga
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, ?-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.
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