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

Su, Hua; Xu, Xiaoling; Yan, Chao; Shi, Yandong; Hu, Yanjie; Dong, Liu; Ying, Songmin; Ying, Kejing; Zhang, Ruifeng

doi:10.1186/s12931-018-0956-z

Cited by 94 publications

(81 citation statements)

References 63 publications

(74 reference statements)

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“…MicroRNAs sponged by the target genes of interest were analyzed. MiR-125a-3p, miR-23a-5p, miR-98-5p, let-7b-5p, let-7a-5p, let-7g-5p, and miR-205 were analyzed because they were reported to be associated with PH (32, 33). We filtered the key mRNAs and miRNAs, and founded that the two circRNAs were the most enriched, which were originated from chr1:204520403-204533534- (Xpo6) and chr7:40223440-40237400- (Tmtc3).…”

Section: Resultsmentioning

confidence: 99%

“…PASMCs and PAECs were isolated using the methods according to previous reports (32, 47, 48). PASMCs and PAECs were cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and 20% FBS for 48h, respectively (32, 49). The cells were incubated in a 37°C, 21% O 2 or 1% O 2 –5% CO 2 humidified incubator.…”

Section: Methodsmentioning

confidence: 99%

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Transcriptome-wide map of m⁶A circRNAs identified in hypoxic pulmonary hypertension rat model

Zhou

et al. 2019

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32Hypoxic pulmonary hypertension (HPH) is a lethal disease. CircRNAs and m 6 A 33 circRNAs have been reported to be associated with cancer progression, but the 34 expression profiling of m 6 A circRNAs has not been identified in HPH. This study was 35 to investigate the transcriptome-wide map of m 6 A circRNAs in HPH. In this study, 36 hypoxia-induced PH rat model was established. Total RNA was extracted and purified 37 from lungs of rats, then circRNAs were detected and annotated by RNA-seq analysis. 38 m 6 A RNA Immunoprecipitation (MeRIP) was performed following rRNA depletion, 39 and RNA-seq library was constructed. CircRNA-miRNA-mRNA co-expression 40 network was also constructed. In vitro, total m 6 A was measured. m 6 A circXpo6 and 41 m 6 A circTmtc3 were detected in pulmonary artery smooth muscle cells (PASMCs) and 42 pulmonary artery endothelial cells (PAECs) exposed to 21% O 2 and 1% O 2 for 48 h, 43 respectively. m 6 A abundance in 166 circRNAs was significantly upregulated and m 6 A 44 abundance in 191 circRNAs was significantly downregulated in lungs of HPH rats. 45 m 6 A abundance in circRNAs was significantly reduced in hypoxia in vitro. m 6 A 46 circRNAs were mainly derived from single exons of protein-coding genes. m 6 A 47 influenced the circRNA-miRNA-mRNA co-expression network in hypoxia. m 6 A 48 circXpo6 and m 6 A circTmtc3 were downregulated in hypoxia. In general, our study 49 firstly identified the transcriptome-wide map of m 6 A circRNAs in HPH. m 6 A level in 50 circRNAs was decreased in lungs of HPH rats and in PASMCs and PAECs exposed to 51 hypoxia. Downregulated or upregulated m 6 A level influenced circRNA-miRNA-52 mRNA co-expression network in HPH. Moreover, we firstly identified two 53 downregulated m 6 A circRNAs in HPH: circXpo6 and circTmtc3. We suggested that 54 m 6 A circRNAs may be used as a potential diagnostic marker or therapy target in the 55 future.56 57 58 59 60 3 61 62 Author summary 63 HPH is a disease with great morbidity and mortality. It is often caused by chronic 64 hypoxic lung diseases, such as chronic obstructive pulmonary disease and interstitial 65 lung diseases. It lacks effective therapy methods so far. CircRNAs are a type of non-66 coding RNAs and can be used as biomarkers because they are differentially enriched in 67 specific cell types or tissues and not easily degraded. m 6 A is identified as the most 68 universal modification on non-coding RNAs in eukaryotes. CircRNAs can be modified 69 by m 6 A. m 6 A circRNAs in HPH is not well understood yet. Here we identify the 70 transcriptome-wide map of m 6 A circRNAs in HPH. We elucidate that m 6 A level in 71circRNAs is decreased in lungs of HPH rats and in PASMCs and PAECs exposed to 72 hypoxia. We find that downregulated or upregulated m 6 A level influences circRNA-73 miRNA-mRNA co-expression network in HPH. Moreover, we are the first to identify 74 two downregulated m 6 A circRNAs in HPH: circXpo6 and circTmtc3. We suggest that 75 m 6 A circRNAs may be used as a potential diagnostic marker or thera...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Transcriptome-wide map of m⁶A circRNAs identified in hypoxic pulmonary hypertension rat model

Zhou

et al. 2019

Preprint

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“…4). H19 then increases AT 1 R expression via sponging let-7b miRNA, which targets AT 1 R. Increased AT 1 R expression then leads to the stimulation of PASMCs proliferation (175). Similarly, hypoxia promotes the expression of lncRNA PAXIP1-AS1.…”

Section: Long Non-coding Rnasmentioning

confidence: 99%

Targeting epigenetic mechanisms as an emerging therapeutic strategy in pulmonary hypertension disease

et al. 2020

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Pulmonary arterial hypertension (PAH) is a multifactorial cardiopulmonary disease characterized by an elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR), which can lead to right ventricular (RV) failure, multi-organ dysfunction, and ultimately to premature death. Despite the advances in molecular biology, the mechanisms underlying pulmonary hypertension (PH) remain unclear. Nowadays, there is no curative treatment for treating PH. Therefore, it is crucial to identify novel, specific therapeutic targets and to offer more effective treatments against the progression of PH. Increasing amounts of evidence suggest that epigenetic modification may play a critical role in the pathogenesis of PAH. In the presented paper, we provide an overview of the epigenetic mechanisms specifically, DNA methylation, histone acetylation, histone methylation, and ncRNAs. As the recent identification of new pharmacological drugs targeting these epigenetic mechanisms has opened new therapeutic avenues, we also discuss the importance of epigenetic-based therapies in the context of PH.

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“…PASMCs and PAECs were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum (FBS) and 20% FBS for 48h, respectively [32,53]…”

Section: Isolation and Hypoxia-treatment Of Pasmcs And Paecsmentioning

confidence: 99%

Transcriptome-wide map of m6A circRNAs identified in a rat model of hypoxia mediated pulmonary hypertension

Wang

et al. 2019

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Background: Hypoxic pulmonary hypertension (HPH) is a lethal disease and lacks effective therapy. CircRNAs play significant roles in physiological process. Recently, circRNAs are found to be m6A-modified. The abundance of circRNAs was influenced by m6A. Furthermore, the significance of m6A circRNAs has not been elucidated in HPH yet. Here we aim to investigate the transcriptome-wide map of m6A circRNAs in HPH. Results: Differentially expressed m6A abundance was detected in lungs of HPH rats. M6A abundance in circRNAs was significantly reduced in hypoxia in vitro. M6A circRNAs were mainly from protein-coding genes spanned single exons in control and HPH groups. Moreover, m6A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. M6A circXpo6 and m6A circTmtc3 were firstly identified to be downregulated in HPH. Conclusion: Our study firstly identified the transcriptome-wide map of m6A circRNAs in HPH. M6A can influence circRNA–miRNA–mRNA network. Furthermore, we firstly identified two HPH-associated m6A circRNAs: circXpo6 and circTmtc3. However, the clinical significance of m6A circRNAs for HPH should be further validated. Key words: m6A circRNAs; hypoxic pulmonary hypertension; m6A circXpo6; m6A circTmtc3

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

Cited by 94 publications

References 63 publications

Transcriptome-wide map of m⁶A circRNAs identified in hypoxic pulmonary hypertension rat model

Transcriptome-wide map of m⁶A circRNAs identified in hypoxic pulmonary hypertension rat model

Targeting epigenetic mechanisms as an emerging therapeutic strategy in pulmonary hypertension disease

Transcriptome-wide map of m6A circRNAs identified in a rat model of hypoxia mediated pulmonary hypertension

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

Cited by 94 publications

References 63 publications

Transcriptome-wide map of m6A circRNAs identified in hypoxic pulmonary hypertension rat model

Transcriptome-wide map of m6A circRNAs identified in hypoxic pulmonary hypertension rat model

Targeting epigenetic mechanisms as an emerging therapeutic strategy in pulmonary hypertension disease

Transcriptome-wide map of m6A circRNAs identified in a rat model of hypoxia mediated pulmonary hypertension

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Transcriptome-wide map of m⁶A circRNAs identified in hypoxic pulmonary hypertension rat model

Transcriptome-wide map of m⁶A circRNAs identified in hypoxic pulmonary hypertension rat model