Long noncoding RNA MALAT1 promotes hepatic steatosis and insulin resistance by increasing nuclear SREBP-1c protein stability

Yan, Caifeng; Chen, Jinfeng; Chen, Nuoqi

doi:10.1038/srep22640

Cited by 161 publications

(173 citation statements)

References 31 publications

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“…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]. These investigations of single lncRNAs provide a further rationale for the analysis of global changes in lncRNA expression in NAFLD and NASH.…”

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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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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“…MALAT1 induced hepatic lipid accumulation and insulin resistance by interacting with SREBP-1c and stabilizing its protein in hepatocytes. 28 Knockdown of MALAT1 effectively reversed lipid aggregation and increased insulin sensitivity in ob/ob mice.…”

Section: Lncrnas In Hepatic Lipid and Glucose Metabolismmentioning

confidence: 93%

Long non-coding RNA in liver metabolism and disease: Current status

Zhao

Liangpunsakul

et al. 2017

Liver Research

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Long non-coding RNAs (lncRNAs) are comprised of RNA transcripts exceeding 200 nucleotides in length but lacking identifiable open reading frames (with rare exceptions). Herein, we highlight emerging evidence demonstrating that lncRNAs are critical regulators of liver metabolic function and diseases. We summarize current knowledges about dysregulated lncRNAs and outline the underlying molecular mechanisms by which lncRNAs control hepatic lipid ad glucose metabolism, as well as cholestatic liver disease. lncLSTR, Lnc18q22.2, SRA, HULC, MALAT1, lncLGR, MEG3, and H19, lncHR1, lnc-HC, APOA1-AS, DYNLRB2-2, and LeXis are included in the discussion.

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“…For example, LncLGRAs, the transcriptional regulatory factor of the hepatic GCK gene, can inhibit the expression of GCK and reduce hepatic glycogen content in mice during fasting [55]. Enhanced expression of lncRNA MALAT1 either in vivo or in vitro activates nuclear SREBP1c expression and induces its intracellular lipid accumulation in mouse hepatocytes [56]. Our previous studies have indicated that significant differentially expressed mRNAs and miRNAs in peak-laying chickens are highly relevant to hepatic lipid metabolism [27,36].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Profile Analysis Reveals an Estrogen Induced LncRNA Associated with Lipid Metabolism and Carcass Traits in Chickens (Gallus Gallus)

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Accumulating evidences have demonstrated that long noncoding RNAs (lncRNA) play important roles in hepatic lipid metabolism in mammals. However, no systematic screening of the potential lncRNAs in the livers of laying hens has been performed, and few studies have been reported concerning the effects of the lncRNAs on lipid metabolism in the livers of chickens during egg-laying period. The purpose of this study was to compare the difference in lncRNA expression in the livers of pre-laying and peak-laying hens at the age of 20 and 30 weeks old by transcriptome sequencing and to investigate the interaction networks among lncRNAs, mRNAs and miRNAs. Moreover, the regulatory mechanism and biological function of lncLTR, a significantly differentially expressed lncRNA in the liver between pre- and peak-laying hens, was explored in vitro and in vivo. Methods: Bioinformatics analyses were conducted to identify the differentially expressed (DE) lncRNAs between the two groups of hens. The target genes of the DE lncRNA were predicated for further functional enrichment. An integrated analysis was performed among the DE lncRNA datasets, DE mRNAs and DE miRNA datasets obtained from the same samples to predict the interaction relationship. In addition, in vivo and in vitro trials were carried out to determine the expression regulation of lncLTR, and polymorphism association analysis was conducted to detect the biological role of ncLTR. Results: A total of 124 DE lncRNAs with a P-value ≤ 0.05 were identified. Among them, 44 lncRNAs including 30 known and 14 novel lncRNAs were significant differentially expressed (SDE) with FDR ≤ 0.05. Thirty-two lncRNAs were upregulated and 12 were downregulated in peak-laying group compared with pre-laying group. The functional enrichment results revealed that target genes of some lncRNAs are involved in the lipid metabolism process. Integrated analysis suggested that some of the genes involved in lipid metabolism might be regulated by both the lncRNA and the miRNA. In addition, an upregulated lncRNA, designated lncLTR, was demonstrated to be induced by estrogen via ERβ signaling. The c242. G>A SNP in lncLTR was significantly associated with chicken carcass weight, evisceration weight, semi-evisceration weight, head weight, double-wing weight, claw weight traits, and blood biochemical index, especially for the blood triglyceride content. Conclusion: A series of lncRNAs associated with lipid metabolism in the livers of chickens were identified by transcriptome sequencing and functional analysis, providing a valuable data resource for further studies on chicken hepatic metabolism activities. LncLTR was regulated by estrogen via ERβ signaling and associated with chicken carcass trait and blood triglyceride content.

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Long noncoding RNA MALAT1 promotes hepatic steatosis and insulin resistance by increasing nuclear SREBP-1c protein stability

Cited by 161 publications

References 31 publications

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

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

Long non-coding RNA in liver metabolism and disease: Current status

Transcriptome Profile Analysis Reveals an Estrogen Induced LncRNA Associated with Lipid Metabolism and Carcass Traits in Chickens (Gallus Gallus)

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