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

Zheng, Jianjian; Yu, Fang; Dong, Peihong; Wu, Limei; Zhang, Yuan; Hu, Yan‐Wei; Zheng, Lei

doi:10.18632/oncotarget.11709

Cited by 77 publications

(62 citation statements)

References 35 publications

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“…For example, Choi et al previously found that leptin promotes the myofibroblastic phenotype in hepatic stellate cells by Hedgehog-enhanced EMT process [6]. Our previous studies demonstrated that lncRNA-PVT1 epigenetically down-regulates PTCH1 expression via competitively binding microRNA-152 (miR-152), contributing to EMT process in liver fibrosis [7]. Therefore, inhibiting EMT process in liver fibrosis may be an effective therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-30a Suppresses the Activation of Hepatic Stellate Cells by Inhibiting Epithelial-to-Mesenchymal Transition

Zheng¹,

Wang²,

Yu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The activation of hepatic stellate cells (HSCs) is considered as a pivotal event in liver fibrosis and epithelial-mesenchymal transition (EMT) process has been reported to be involved in HSC activation. It is known that microRNAs (miRNAs) play a pro-fibrotic or anti-fibrotic role in HSC activation. Recently, emerging studies show that miR-30a is down-regulated in human cancers and over-expression of miR-30a inhibits tumor growth and invasion via suppressing EMT process. However, whether miR-30a could regulate EMT process in HSC activation is still unclear. Methods: miR-30a expression was quantified using real-time PCR in carbon tetrachloride (CCl₄)-induced rat liver fibrosis, activated HSCs and patients with cirrhosis. Roles of miR-30a in liver fibrosis in vivo and in vitro were also analyzed. Luciferase activity assays were performed to examine the binding of miR-30a to the 3′-untranslated region of snail family transcriptional repressor 1 (Snai1). Results: miR-30a was down-regulated in human cirrhotic tissues. In CCl₄ rats, reduced miR-30a was found in fibrotic liver tissues as well as isolated HSCs. There was a significant reduction in miR-30a in primary HSCs during culture days. miR-30a over-expression resulted in the suppression of CCl₄-induced liver fibrosis. Restoration of miR-30a led to the inhibition of HSC activation including cell proliferation, α-SMA and collagen expression. Notably, miR-30a inhibited EMT process, with a reduction in TGF-β1 and Vimentin as well as an increase in GFAP and E-cadherin. miR-30a induced a significant reduction in Snai1 protein expression when compared with the control. Interestingly, Snail protein expression was increased during liver fibrosis, indicating that there may be a negative correlation between miR-30a level and Snai1 protein expression. Further studies demonstrated that Snai1 was a target of miR-30a. Conclusion: Our results suggest that miR-30a inhibits EMT process, at least in part, via reduction of Snai1, leading to the suppression of HSC activation in liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-30a Suppresses the Activation of Hepatic Stellate Cells by Inhibiting Epithelial-to-Mesenchymal Transition

Zheng¹,

Wang²,

Yu³

et al. 2018

Cell Physiol Biochem

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“…72 Consistently, its depletion in gastric cancer promotes EMT phenotypic changes in cells, and these changes are also seen at the transcriptome level. 73 79 Likewise, the overexpression of PVT1 resulted in an increase of Snail and ZEB1 expression in pancreatic cancer (Figure 2). 80…”

Section: Tumor Driversmentioning

confidence: 88%

Emerging roles of long non‐coding RNA in cancer

Calle¹,

Kawamura

Yamamoto³

et al. 2018

Cancer Science

504

414

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Since comprehensive analysis of the mammalian genome revealed that the majority of genomic products are transcribed in long non‐coding RNA (lncRNA), increasing attention has been paid to these transcripts. The applied next‐generation sequencing technologies have provided accumulating evidence of dysregulated lncRNA in cancer. The implication of this finding can be seen in many forms and at multiple levels. With impacts ranging from integrating chromatin remodeling complexes to regulating transcription and post‐transcriptional processes, aberrant expression of lncRNA may have repercussions in cell proliferation, tumor progression or metastasis. lncRNA may act as enhancers, scaffolds or decoys by physically interacting with other RNA species or proteins, resulting in a direct impact on cell signaling cascades. Even though their functional classification is well‐established in the context of cancer, clearer characterization in terms of their phenotypic outputs is needed to optimize and identify suitable candidates that enable the development of new therapeutic strategies and the design of novel diagnostic approaches. The present article aims to outline different cancer‐associated lncRNA according to their contribution to tumor suppression or tumor promotion based on their most current functional annotations.

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“…Accumulating evidence demonstrated that hepatocytes epithelial–mesenchymal transition (EMT) as an important biological process has been involved in inducing or promoting a variety of cellular activities including liver fibrosis (Zhang et al, ; Zheng et al, ). However, little is known about the molecule mechanisms responsible for the development of liver fibrosis, and thus no specific anti‐fibrotic medical therapy exists.…”

Section: Discussionmentioning

confidence: 99%

Advanced oxidation protein products induce hepatocyte epithelial–mesenchymal transition via a ROS‐dependent, TGF‐β/Smad signaling pathway

Sun

Xie

Zhang

et al. 2017

Cell Biology International

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Epithelial-mesenchymal transition (EMT) occurs during the progression of liver fibrosis in response to chronic liver injury. However, the molecular mechanism underlying the regulation of hepatocyte EMT remains unclear. The aim of this study was to determine whether advanced oxidation protein products (AOPP) had an effect on hepatocyte EMT. The human L02 hepatocyte cell line and hepatocytes from normal Sprague-Dawley rats were challenged with AOPP treatment in both in vitro and in vivo studies. The expression of cell and molecular markers of EMT in L02 hepatocytes were studied using Western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. Hepatocyte migratory potential was analyzed using a wound healing assay. Intracellular reactive oxygen species (ROS) were detected using the dichlorofluorescein (DCF) assay. In liver tissue sections, expression of EMT markers was evaluated using immunohistochemistry, and collagen was assessed using histochemical staining with Masson's trichrome. The findings were that AOPP treatment resulted in EMT in hepatocytes, which was associated with reduced expression of E-cadherin, increased expression of vimentin, increased deposition of collagen protein, and enhanced cell migration in vivo and in vitro. AOPP was also found to promote migration in L02 cells, and to promote the production of ROS and the activation of TGF-βR and Smad signaling. Inhibition of the generation of intracellular ROS and TGF-β receptor blocking could reverse AOPP-induced EMT in hepatocytes. This study has identified a novel mechanism in the regulation of hepatocyte EMT, and the findings may have implications for the control of liver fibrosis.

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

Cited by 77 publications

References 35 publications

MicroRNA-30a Suppresses the Activation of Hepatic Stellate Cells by Inhibiting Epithelial-to-Mesenchymal Transition

MicroRNA-30a Suppresses the Activation of Hepatic Stellate Cells by Inhibiting Epithelial-to-Mesenchymal Transition

Emerging roles of long non‐coding RNA in cancer

Advanced oxidation protein products induce hepatocyte epithelial–mesenchymal transition via a ROS‐dependent, TGF‐β/Smad signaling pathway

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