Long non-coding RNA APTR promotes the activation of hepatic stellate cells and the progression of liver fibrosis

Yu, Fang; Zheng, Jianjian; Mao, Yuqing; Dong, Peihong; Li, Guojun; Lu, Zhongqiu; Guo, Chuanyong; Liu, Zhanju; Fan, Xiaoming

doi:10.1016/j.bbrc.2015.05.124

Cited by 68 publications

(60 citation statements)

References 23 publications

(18 reference statements)

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“…14 We previously found that Alu-mediated p21 transcriptional regulator (APTR) contributes to HSC activation. 15 Homeobox (HOX) transcript antisense RNA (HOTAIR), as a lincRNA, is often deregulated in human neoplasia. 16,17 Accumulating studies have indicated that HOTAIR is upregulated in cancers including HCC.…”

Section: Introductionmentioning

confidence: 99%

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

et al. 2017

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Section: Introductionmentioning

confidence: 99%

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

et al. 2017

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“…In addition to investigations of individual lncRNAs, including MEG3 [31], APTR [32], and MALAT1 [33], to our knowledge, only a single study has reported a genome-wide analysis of lncRNAs in human liver tissue with NAFLD [34]. In that study, liver tissue was obtained from ten patients with gallbladder stones, five with NAFLD, and none with metabolic disease (i.e., T2D).…”

Section: Discussionmentioning

confidence: 99%

“…For example, levels of the lncRNA, maternally expressed gene 3 ( MEG3 ), were significantly decreased in a CCl 4 -induced mouse liver fibrosis model and in human liver fibrosis of undisclosed etiology [31]. Another lncRNA, Alu -mediated p21 transcriptional regulator ( APTR ), was found to be upregulated in human cirrhosis and activated hepatic stellate cells [32]. Expression of metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ) was increased in livers of ob/ob mice, as well as hepatocytes exposed to palmitate [33].…”

Section: Introductionmentioning

confidence: 99%

Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells

Leti

Legendre

Still

et al. 2017

Translational Research

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In the present study, we sought to identify lncRNA expression profiles in NASH patients with histological evidence of lobular inflammation and advanced fibrosis. We profiled lncRNA expression using RNA-sequencing of wedge liver biopsies from 24 NAFLD patients with normal liver histology, 53 NAFLD patients with lobular inflammation, and 65 NAFLD patients with advanced fibrosis. Transcript profiling identified 4432 and 4057 differentially expressed lncRNAs in comparisons of normal tissue with lobular inflammation and fibrosis samples, respectively. Functional enrichment analysis revealed lncRNA participation in TGFB1 and TNF signaling, insulin resistance, and extracellular matrix maintenance. Several lncRNAs were highly expressed in fibrosis relative to normal tissue, including nuclear paraspeckle assembly transcript 1 (NEAT1), hepatocellular carcinoma upregulated lncRNA (HULC), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). Two potential target mRNAs, syndecan 4 (SDC4) and C-X-C motif chemokine ligand 5 (CXCL5) were identified for HULC and MALAT1, respectively, but only CXCL5 showed differential expression among the different histological classes. Knockdown of MALAT1 expression reduced CXCL5 transcript and protein levels by 50% and 30%, respectively, in HepG2 cells. Expression of MALAT1 and CXCL5 was upregulated in activated hepatic stellate (LX-2) cells compared to cells in the quiescent state, and MALAT1 expression was regulated by hyperglycemia and insulin in HepG2 cells, but only by insulin in LX-2 cells. Dysregulated lncRNA expression is associated with inflammation and fibrosis in NASH. Functionally relevant differences in MALAT1 expression may contribute to the development of fibrosis in NASH through mechanisms involving inflammatory chemokines.

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“…Recent studies have shown that many lncRNAs including H19 [12], lincRNA-p21 [13], GAS5 [19], MALAT1 [20] and APTR [21], are involved in the progression of liver fibrosis. To investigate whether these lncRNAs play a role in the effects of Sal B on HSC activation, the expressions of H19, lincRNA-p21, MALAT1, APTR and GAS5 were examined in Sal B-treated primary HSCs.…”

Section: Resultsmentioning

confidence: 99%

LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p

Guo

Chen

et al. 2017

Cell Physiol Biochem

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Background/Aims: It is known that the activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Aberrant activated Wnt/β-catenin pathway is known to accelerate the development of liver fibrosis. microRNAs (miRNAs)-mediated Wnt/β-catenin pathway has been reported to be involved in HSC activation during liver fibrosis. However, whether long noncoding RNAs (lncRNAs) regulate Wnt/β-catenin pathway during HSC activation still remains unclear. Methods: Long intergenic noncoding RNA-p21 (lincRNA-p21) expression was detected in Salvianolic acid B (Sal B)-treated cells. Effects of lincRNA-p21 knockdown on HSC activation and Wnt/β-catenin pathway activity were analyzed in Sal B-treated cells. In lincRNA-p21-overexpressing cells, effects of miR-17-5p on HSC activation and Wnt/β-catenin pathway activity were examined. Results: LincRNA-p21 expression was up-regulated in HSCs after Sal B treatment. In primary HSCs, lincRNA-p21 expression was down-regulated at Day 5 relative to Day 2. Sal B-inhibited HSC activation including the reduction of cell proliferation, α-smooth muscle actin (α-SMA) and type I collagen was inhibited by lincRNA-p21 knockdown. Sal B-induced Wnt/β-catenin pathway inactivation was blocked down by loss of lincRNA-p21. Notably, lincRNA-p21, confirmed as a target of miR-17-5p, suppresses miR-17-5p level. Lack of the miR-17-5p binding site in lincRNA-p21 prevents the suppression of miR-17-5p expression. In addition, the suppression of HSC activation and Wnt/β-catenin pathway induced by lincRNA-p21 overexpression was almost inhibited by miR-17-5p. Conclusion: We demonstrate that lincRNA-p21-inhibited Wnt/β-catenin pathway is involved in the effects of Sal B on HSC activation and lincRNA-p21 suppresses HSC activation, at least in part, via miR-17-5p-mediated-Wnt/β-catenin pathway.

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Long non-coding RNA APTR promotes the activation of hepatic stellate cells and the progression of liver fibrosis

Cited by 68 publications

References 23 publications

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells

LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p

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