Microarray profiling of long non-coding RNAs associated with idiopathic pulmonary arterial hypertension

Han, Bing; Bu, Peili; Xiao, Meng; Hou, Xiaoyang

doi:10.3892/etm.2017.4355

Cited by 12 publications

(10 citation statements)

References 36 publications

(39 reference statements)

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“…Only a few recent studies have shown their contribution to vascular smooth muscle cell proliferation or apoptosis (e.g. MALAT1 or LnRPT ) and only one study has investigated the lncRNA profile in PAH patients using peripheral blood lymphocytes . Here, we have demonstrated that transcriptional reprogramming in small remodelled arteries (intima and media) is associated with a specific lncRNA expression profile in IPAH.…”

Section: Discussionmentioning

confidence: 70%

Long non‐coding RNAs influence the transcriptome in pulmonary arterial hypertension: the role of PAXIP1‐AS1

Jandl

Puthenparampil

Marsh

et al. 2019

The Journal of Pathology

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In idiopathic pulmonary arterial hypertension (IPAH), global transcriptional changes induce a smooth muscle cell phenotype characterised by excessive proliferation, migration, and apoptosis resistance. Long non‐coding RNAs (lncRNAs) are key regulators of cellular function. Using a compartment‐specific transcriptional profiling approach, we sought to investigate the link between transcriptional reprogramming by lncRNAs and the maladaptive smooth muscle cell phenotype in IPAH. Transcriptional profiling of small remodelled arteries from 18 IPAH patients and 17 controls revealed global perturbations in metabolic, neuronal, proliferative, and immunological processes. We demonstrated an IPAH‐specific lncRNA expression profile and identified the lncRNA PAXIP1‐AS1 as highly abundant. Comparative transcriptomic analysis and functional assays revealed an intrinsic role for PAXIP1‐AS1 in orchestrating the hyperproliferative and migratory actions of IPAH smooth muscle cells. Further, we showed that PAXIP1‐AS1 mechanistically interferes with the focal adhesion axis via regulation of expression and phosphorylation of its downstream target paxillin. Overall, we show that changes in the lncRNA transcriptome contribute to the disease‐specific transcriptional landscape in IPAH. Our results suggest that lncRNAs, such as PAXIP1‐AS1, can modulate smooth muscle cell function by affecting multiple IPAH‐specific transcriptional programmes. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 70%

Long non‐coding RNAs influence the transcriptome in pulmonary arterial hypertension: the role of PAXIP1‐AS1

Jandl

Puthenparampil

Marsh

et al. 2019

The Journal of Pathology

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“…Dys-regulated expression of miRNAs, mRNAs and lncRNAs has been reported to play a critical role in the progression of PAH 38,39 . However, an integrated analysis of the potential interactions between these different types of RNA molecules is only beginning to emerge 34,40 .…”

Section: Discussionmentioning

confidence: 99%

Analysis of lncRNA-miRNA-mRNA Interactions in Hyper-proliferative Human Pulmonary Arterial Smooth Muscle Cells

Chinnappan

Gunewardena

Chalise

et al. 2019

Sci Rep

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We previously reported enhanced proliferation of smooth muscle cells on the combined exposure of HIV proteins and cocaine leading to the development of HIV-pulmonary arterial hypertension. Here, we attempt to comprehensively understand the interactions between long noncoding RNAs (lncRNAs), mRNAs and micro-RNAs (miRNAs) to determine their role in smooth muscle hyperplasia. Differential expression of lncRNAs, mRNAs and miRNAs were obtained by microarray and small-RNA sequencing from HPASMCs treated with and without cocaine and/or HIV-Tat. LncRNA to mRNA associations were conjectured by analyzing their genomic proximity and by interrogating their association to vascular diseases and cancer co-expression patterns reported in the relevant databases. Neuro-active ligand receptor signaling, Ras signaling and PI3-Akt pathway were among the top pathways enriched in either differentially expressed mRNAs or mRNAs associated to lncRNAs. HPASMC with combined exposure to cocaine and Tat (C + T) vs control identified the following top lncRNA-mRNA pairs, ENST00000495536-HOXB13, T216482-CBL, ENST00000602736-GDF7, and, TCONS_00020413-RND1. Many of the down-regulated miRNAs in the HPASMCs treated with C + T were found to be anti-proliferative and targets of up-regulated lncRNAs targeting up-regulated mRNAs, including down-regulation of miR-185, -491 and up-regulation of corresponding ENST00000585387. Specific knock down of the selected lncRNAs highlighted the importance of non-coding RNAs in smooth muscle hyperplasia.

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“…Currently, some lncRNAs are reported to be associated with PAH. 362 lncRNAs were reported to be differentially expressed in HPH [19], and 2511 lncRNAs were found to be aberrantly expressed in idiopathic PAH [20]. The lncRNA TCONS_00034812 was identified to modulate pulmonary vascular remodeling via MAPK signaling [21].…”

Section: Introductionmentioning

confidence: 99%

LncRNA H19 promotes the proliferation of pulmonary artery smooth muscle cells through AT1R via sponging let-7b in monocrotaline-induced pulmonary arterial hypertension

Yan

et al. 2018

Respir Res

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BackgroundPulmonary arterial hypertension (PAH) is related to inflammation, and the lncRNA H19 is associated with inflammation. However, whether PDGF-BB-H19-let-7b-AT1R axis contributes to the pathogenesis of PAH has not been thoroughly elucidated to date. This study investigated the role of H19 in PAH and its related mechanism.MethodsIn the present study, SD rats, C57/BL6 mice and H19−/− mice were injected with monocrotaline (MCT) to establish a PAH model. H19 was detected in the cytokine-stimulated pulmonary arterial smooth muscle cells (PASMCs), serum and lungs of rats/mice. H19 overexpression and knockdown experiments were also conducted. A dual luciferase reporter assay was used to explore whether let-7b is a sponge miRNA of H19, and AT1R is a novel target of let-7b. A CCK-8 assay and flow cytometry were used to analyse cell proliferation.ResultsThe results showed that H19 was highly expressed in the serum and lungs of MCT-induced rats/mice, and H19 was upregulated by PDGF-BB in vitro. H19 upregulated AT1R expression via sponging miRNA let-7b following PDGF-BB stimulation. AT1R is a novel target of let-7b. Moreover, the overexpression of H19 and AT1R could facilitate PASMCs proliferation in vitro. H19 knockout protected mice from pulmonary artery remodeling and PAH following MCT treatment.ConclusionOur study showed that H19 is highly expressed in MCT-induced rodent lungs and upregulated by PDGF-BB. The H19-let-7b-AT1R axis contributed to the pathogenesis of PAH by stimulating PASMCs proliferation. The H19 knockout had a protective role in the development of PAH. H19 may be a potential tar-get for the treatment of PAH.

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Microarray profiling of long non-coding RNAs associated with idiopathic pulmonary arterial hypertension

Cited by 12 publications

References 36 publications

Long non‐coding RNAs influence the transcriptome in pulmonary arterial hypertension: the role of PAXIP1‐AS1

Long non‐coding RNAs influence the transcriptome in pulmonary arterial hypertension: the role of PAXIP1‐AS1

Analysis of lncRNA-miRNA-mRNA Interactions in Hyper-proliferative Human Pulmonary Arterial Smooth Muscle Cells

LncRNA H19 promotes the proliferation of pulmonary artery smooth muscle cells through AT1R via sponging let-7b in monocrotaline-induced pulmonary arterial hypertension

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