LncRNA<i>NEAT1</i>: Shedding light on mechanisms and opportunities in liver diseases

Bu, Fang‐tianang‐tian; Wang, Ao; Zhu, Yanan; You, Hongmei; Zhang, Ya‐fei; Meng, Xiao‐Ming; Huang, Cheng; Li, Jun

doi:10.1111/liv.14629

Cited by 54 publications

(42 citation statements)

References 122 publications

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“…Liu et al [ 62 ] reported that BMMSCs transfected with ANGPT1 had therapeutic effects on hyperoxia induced optic nerve injury. With respect to non-coding RNAs in the networks, NEAT1 has been proven to act as an oncogene in multiple cancers by binding to various miRNAs [ 63 , 64 ]. LINC02595 could promote colorectal cancer progression by inhibiting miR-203b-3p activity [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients

et al. 2021

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Background Mesenchymal stem cells including adipose-derived stem cells (ASCs) have a considerable potential in the field of translational medicine. Unfortunately, multiple factors (e.g., older age, co-existing diabetes, and obesity) may impair cellular function, which hinders the overall effectiveness of autologous stem cell therapy. Noncoding RNAs—including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)—have been shown to play important roles in stem cell biology. However, the overall diabetes-related and aging-related expression patterns and interactions of these RNAs in ASCs remain unknown. Method The phenotypes and functions of ASCs isolated from diabetic (D-ASCs), old (O-ASCs), and young (Y-ASCs) donors were evaluated by in vitro assays. We conducted high-throughput RNA sequencing (RNA-seq) in these ASCs to identify the differentially expressed (DE) RNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analyses were performed to investigate mRNAs with significant differences among groups. The lncRNA- or circRNA-associated competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses and real-time polymerase chain reaction (RT-PCR) results. The miR-145-5p mimics were transfected into O-ASCs and verified by PCR. Results ASCs from diabetic and old donors showed inferior migration ability and increased cellular senescence. Furthermore, O-ASCs have decreased capacities for promoting endothelial cell angiogenesis and fibroblast migration, compared with Y-ASCs. The DE miRNAs, mRNAs, lncRNAs, and circRNAs were successfully identified by RNA-seq in O-ASCs vs. Y-ASCs and D-ASCs vs. O-ASCs. GO and KEGG analyses demonstrated that DE mRNAs were significantly enriched in aging and cell senescence terms separately. PPI networks revealed critical DE mRNAs in the above groups. RNAs with high fold changes and low p values were validated by PCR. ceRNA networks were constructed based on bioinformatics analyses and validated RNAs. Additionally, the lncRNA RAET1E-AS1–miR-145-5p–WNT11/BMPER axis was validated by PCR and correlation analyses. Finally, the overexpression of miR-145-5p was found to rejuvenate O-ASCs phenotype and augment the functionality of these cells. Conclusion Our research may provide insights regarding the underlying mechanisms of ASC dysfunction; it may also offer novel targets for restoring therapeutic properties in ASCs.

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Section: Discussionmentioning

confidence: 99%

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients

et al. 2021

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“…Previous studies have shown that the networks between lncRNAs and miRNAs performed important regulatory roles in the pathogenesis of various human cancers and fibrotic diseases [ 31 ]. Among quantities of lncRNAs relevant to fibrogenesis, NEAT1 is a lncRNA originally serving as mammary development regulator, which was later verified to be intimately associated with fibrotic diseases [ 32 ]. Although NEAT1 was shown to regulate liver fibrosis and HSCs activation, the specific signaling pathways mediating its roles in liver fibrosis remain poorly known.…”

Section: Discussionmentioning

confidence: 99%

miR-139-5p sponged by LncRNA NEAT1 regulates liver fibrosis via targeting β-catenin/SOX9/TGF-β1 pathway

Wang

Song

et al. 2021

Cell Death Discov.

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Liver fibrosis is a patho-physiological process which can develop into cirrhosis, and hepatic carcinoma without intervention. Our study extensively investigated the mechanisms of lncRNA NEAT1 and miR-139-5p in regulating liver fibrosis progression. Our results demonstrated that the expression of lncRNA NEAT1 was increased and the expression of miR-139-5p was decreased in fibrotic liver tissues. LncRNA NEAT1 could sponge miR-139-5p and promoted hepatic stellate cells (HSCs) activation by directly inhibiting the expression of miR-139-5p. The co-localization of lncRNA NEAT1 with miR-139-5p was shown in the cytosols of activated HSCs. miR-139-5p upregulation could suppress the expression of β-catenin. The overexpression of β-catenin promoted HSCs activation. Moreover, we found that β-catenin could interact with SOX9 promoted HSCs activation. Our further studies demonstrated that SOX9 could bind with the TGF-β1 promoter and promoted the transcription activity of TGF-β1. The upregulation of TGF-β1 further promoted HSCs activation. In vivo study also suggested that lncRNA NEAT1 knockdown and miR-139-5p overexpression alleviated murine liver fibrosis. LncRNA NEAT1 exacerbated liver fibrosis by suppressing the expression of miR-139-5p. Collectively, our study suggested that miR-139-5p sponged by lncRNA NEAT1 regulated liver fibrosis via targeting β-catenin/SOX9/TGF-β1 Pathway.

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“…Liu et al and colleagues [56] also illuminated that BMMSCs transfected with ANGPT1 had therapeutic effects on hyperoxia induced optic nerve injury. As for non-coding RNAs in the networks, NEAT1 have been proven to act as an oncogene in multiple cancers via binding various miRNAs [57,58]. LINC02595 could promote colorectal cancer progression by inhibiting miR-203b-3p…”

Section: Discussionmentioning

confidence: 99%

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose stem cells from diabetic, old and young patients

Ren

Xiong

Chen

et al. 2021

Preprint

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BackgroundMesenchymal stem cells including adipose stem cells (ASCs) have a huge potential in the field of translational medicine. Unfortunately, multiple factors including older age, co-existing diabetes and obesity may impair cellular function, which hinders the overall effectiveness of autologous stem cell therapy. Noncoding RNAs including microRNAs (miRNA), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been demonstrated to play an important role in stem cell biology. However, the whole expression pattern and interaction of these RNAs in ASCs related to diabetes and aging remain unknown.MethodEdU, transwell and β-galactosidase staining assays were performed to assess the proliferation, migration and senescence of ASCs isolated from diabetic (D-ASCs), old (O-ASCs), and young (Y-ASCs) donators. The abilities of these ASCs modulating endothelial cells and fibroblasts functions were evaluated by tube formation and wound scratch assays. We conducted high-throughput RNA sequencing (RNA-seq) in these ASCs to uncover the differentially expressed (DE) RNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interactions (PPI) analyses were performed to interpret the mRNAs with significant differences. The lncRNAs or circRNAs associated competing endogenous RNA (ceRNA) networks were constructed based on the bioinformatic analyses and real-time polymerase chain reaction (RT-PCR) results. The miR-145-5p mimics were transfected into old ASCs and verified by PCR.ResultsASCs from diabetic and old donators showed inferior migration ability and increased cellular senescence. Besides, old ASCs have decreased capacities for promoting endothelial cells angiogenesis and fibroblasts migration comparing to young ASCs. The DE miRNAs, mRNAs, lncRNAs and circRNAs were successfully identified by RNA-seq in O-ASCs vs Y-ASCs and D-ASCs vs O-ASCs. GO and KEGG analyses demonstrated DE mRNAs were significantly enriched in aging and cell senescence terms separately. PPI networks performed critical DE mRNAs in above groups. MiRNAs with high fold change and low p value were validated by PCR. The four ceRNA networks were conducted based on the bioinformatic analyses and validated miRNAs. The selected mRNAs, lncRNAs and circRNAs in PPI and ceRNA networks were further evaluated by PCR. Then, the ceRNA subnetworks were constructed based on above validated RNAs. In addition, the lncRNA RAET1E-AS1 - miR-145-5p - WNT11/BMPER axis was selected and validated by the PCR and correlation analyses. Finally, overexpression of miR-145-5p could rejuvenate old ASCs phenotype and augment their abilities for modulating endothelial cells and fibroblasts functions.ConclusionTaken together, our research may provide new clues to unveil the underlying mechanisms of ASCs dysfunction, and disclose novel targets for restoring their therapeutic properties.

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LncRNANEAT1: Shedding light on mechanisms and opportunities in liver diseases

Cited by 54 publications

References 122 publications

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients

miR-139-5p sponged by LncRNA NEAT1 regulates liver fibrosis via targeting β-catenin/SOX9/TGF-β1 pathway

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose stem cells from diabetic, old and young patients

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