scholarly journals Construction and analysis of the abnormal lncRNA-miRNA-mRNA network in hypoxic pulmonary hypertension

2021 ◽  
Author(s):  
Jie Liu ◽  
Yishu Deng ◽  
Zeqin Fan ◽  
Shuanglan Xu ◽  
Li Wei ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Cellular Response ◽  
High Throughput Sequencing ◽  
Interleukin 1 ◽  
Signalling Pathway ◽  
Receptor Interaction ◽  
Hypoxic Pulmonary Hypertension ◽  
Hypoxia Exposure ◽  
Receptor Signalling ◽  
Non Coding Rnas

The incidence of hypoxic pulmonary hypertension (HPH) is increasing. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) play an important role in HPH, but the functions and mechanism have yet to be fully elucidated. In this study, we established an HPH rat model with 8 h of hypoxia exposure (10% O2) per day for 21 days. High-throughput sequencing identified 60 differently expressed (DE) lncRNAs, 20 DE miRNAs and 695 DE mRNAs in rat lung tissue. qRT-PCR verified the accuracy of the results. Immune response, inflammatory response, leukocyte migration, cell cycle, cellular response to interleukin-1, IL-17 signalling pathway, cytokine-cytokine receptor interaction and Toll-like receptor signalling pathway were significantly enriched in DE mRNAs. According to the theory of competing endogenous RNA (ceRNA) networks, lncRNA-miRNA-mRNA network was constructed by Cytoscape software, including 7 lncRNAs, 16 miRNAs and 144 mRNAs. The results suggested that seven DE lncRNAs (Ly6l, AABR07038849.2, AABR07069008.2, AABR07064873.1, AABR07001382.1, AABR07068161.1 and AABR07060341.2) could serve as molecular sponges of the corresponding miRNAs and play a major role in HPH.

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

2019 ◽  
Author(s):  
Hua Su ◽  
Lin Zhou ◽  
Na Li ◽  
Guowen Wang ◽  
Lingfang Wu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Rat Model ◽  
Lung Diseases ◽  
Diagnostic Marker ◽  
Rna Seq ◽  
Hypoxic Pulmonary Hypertension ◽  
Non Coding Rnas ◽  
Therapy Target

AbstractHypoxic pulmonary hypertension (HPH) is a lethal disease. CircRNAs and m6A circRNAs have been reported to be associated with cancer progression, but the expression profiling of m6A circRNAs has not been identified in HPH. This study was to investigate the transcriptome-wide map of m6A circRNAs in HPH. In this study, hypoxia-induced PH rat model was established. Total RNA was extracted and purified from lungs of rats, then circRNAs were detected and annotated by RNA-seq analysis. m6A RNA Immunoprecipitation (MeRIP) was performed following rRNA depletion, and RNA-seq library was constructed. CircRNA–miRNA–mRNA co-expression network was also constructed. In vitro, total m6A was measured. m6A circXpo6 and m6A circTmtc3 were detected in pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs) exposed to 21% O2 and 1% O2 for 48 h, respectively. m6A abundance in 166 circRNAs was significantly upregulated and m6A abundance in 191 circRNAs was significantly downregulated in lungs of HPH rats. m6A abundance in circRNAs was significantly reduced in hypoxia in vitro. m6A circRNAs were mainly derived from single exons of protein-coding genes. m6A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. m6A circXpo6 and m6A circTmtc3 were downregulated in hypoxia. In general, our study firstly identified the transcriptome-wide map of m6A circRNAs in HPH. m6A level in circRNAs was decreased in lungs of HPH rats and in PASMCs and PAECs exposed to hypoxia. Downregulated or upregulated m6A level influenced circRNA–miRNA–mRNA co-expression network in HPH. Moreover, we firstly identified two downregulated m6A circRNAs in HPH: circXpo6 and circTmtc3. We suggested that m6A circRNAs may be used as a potential diagnostic marker or therapy target in the future.Author summaryHPH is a disease with great morbidity and mortality. It is often caused by chronic hypoxic lung diseases, such as chronic obstructive pulmonary disease and interstitial lung diseases. It lacks effective therapy methods so far. CircRNAs are a type of non-coding RNAs and can be used as biomarkers because they are differentially enriched in specific cell types or tissues and not easily degraded. m6A is identified as the most universal modification on non-coding RNAs in eukaryotes. CircRNAs can be modified by m6A. m6A circRNAs in HPH is not well understood yet. Here we identify the transcriptome-wide map of m6A circRNAs in HPH. We elucidate that m6A level in circRNAs is decreased in lungs of HPH rats and in PASMCs and PAECs exposed to hypoxia. We find that downregulated or upregulated m6A level influences circRNA– miRNA–mRNA co-expression network in HPH. Moreover, we are the first to identify two downregulated m6A circRNAs in HPH: circXpo6 and circTmtc3. We suggest that m6A circRNAs may be used as a potential diagnostic marker or therapy target in the future.

scholarly journals N7-methylguanosine modification of lncRNAs in a rat model of hypoxic pulmonary hypertension: a comprehensive analysis

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Huan Wang ◽  
Ren Biao Chen ◽  
Si Ni Zhang ◽  
Rui Feng Zhang
Keyword(s):  
Pulmonary Hypertension ◽  
Clinical Significance ◽  
Rat Model ◽  
Critical Role ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Hypoxic Pulmonary Hypertension ◽  
Non Coding Rnas ◽  
First Time

Abstract Background Long non-coding RNAs (lncRNAs) play a critical role in the pathogenesis of hypoxic pulmonary hypertension (HPH). The role of N7-methylguanosine (m7G) modification in lncRNAs has received increased attentions in recent years. However, the m7G-methylation of lncRNA in HPH has yet to be determined. We have therefore performed a transcriptome-wide analysis of m7G lncRNAs in HPH. Results Differentially-expressed m7Gs were detected in HPH, and m7G lncRNAs were significantly upregulated compared with non-m7G lncRNAs in HPH. Importantly, this was the first time that the upregulated m7G lncXR_591973 and m7G lncXR_592398 were identified in HPH. Conclusion This study provides the first m7G transcriptome-wide analysis of HPH. Importantly, two HPH-associated m7G lncRNAs were identified, although their clinical significance requires further validation.

scholarly journals A Novel Mechanism of Action of Histone Deacetylase Inhibitor Chidamide: Enhancing the Chemotaxis Function of Circulating PD-1(+) Cells From Patients With PTCL

2021 ◽  
Vol 11 ◽  
Author(s):  
Chong Wei ◽  
Shaoxuan Hu ◽  
Mingjie Luo ◽  
Chong Chen ◽  
Wei Wang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Histone Deacetylase ◽  
Cellular Response ◽  
Kegg Pathway ◽  
Checkpoint Inhibitors ◽  
Interleukin 1 ◽  
Innate Immune ◽  
Receptor Interaction ◽  
Gene Concept ◽  
Concept Network

BackgroundPeripheral T‐cell lymphomas (PTCLs) are a heterogeneous group of neoplasms characterized by a poor prognosis. Histone deacetylase (HDAC) inhibitors have emerged as novel therapeutic agents for PTCLs. In this study, we aimed to explore the immunomodulatory effect of the HDAC inhibitor chidamide on circulating PD-1(+) cells from patients with PTCL, as well as its correlation with treatment response.MethodsWe enrolled newly diagnosed patients with PTCLs treated with a combination of chidamide and chemotherapy. Gene expression profile analysis was performed on peripheral blood PD-1(+) cells, both at baseline and at the end of treatment. A list of differentially expressed genes (DEGs) was identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological implications of the DEGs. A gene concept network was constructed to identify the key DEGs for further PCR verification.ResultsA total of 302 DEGs were identified in the complete remission (CR) group, including 162 upregulated and 140 downregulated genes. In contrast, only 12 DEGs were identified in the non-CR group. GO analysis revealed that these upregulated DEGs were mainly involved in chemokine activity, cell chemotaxis, and cellular response to interleukin-1 and interferon-γ. Furthermore, KEGG pathway analysis showed that these DEGs were enriched in cytokine-cytokine receptor interaction and chemokine signaling pathways. The innate immune signaling pathways, including the Toll-like and NOD-like receptor signaling pathways, were also influenced. The gene concept network revealed that the key upregulated genes belonged to the C-C chemokine family.ConclusionOur results showed that chidamide treatment notably enhanced the expression of genes associated with chemokine activity and chemotaxis function of circulating PD-1(+) cells. By recruiting immune cells and improving the innate immune function of PD-1(+) cells, chidamide may reshape the tumor microenvironment to an anti-tumor phenotype and synergize with checkpoint inhibitors.

Inhibition of mTOR by rapamycin does not improve hypoxic pulmonary hypertension-induced right heart failure in old mice

2021 ◽  
pp. 111395
Author(s):  
Benjamin D. McNair ◽  
Jacob A. Schlatter ◽  
Ross F. Cook ◽  
Musharraf Yusifova ◽  
Danielle R. Bruns
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Right Heart Failure ◽  
Right Heart ◽  
Hypoxic Pulmonary Hypertension ◽  
Old Mice

scholarly journals Identification of the pyroptosis‑related prognostic gene signature and the associated regulation axis in lung adenocarcinoma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Wanli Lin ◽  
Ying Chen ◽  
Bomeng Wu ◽  
Ying chen ◽  
Zuwei Li
Keyword(s):  
Lung Adenocarcinoma ◽  
Microsatellite Instability ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
Signalling Pathway ◽  
Functional Enrichment ◽  
Receptor Signalling ◽  
Cerna Network ◽  
Prognostic Gene ◽  
Mutation Burden

AbstractLung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. Pyroptosis could regulate tumour cell proliferation, invasion, and metastasis, thereby affecting the prognosis of cancer patients. However, the role of pyroptosis-related genes (PRGs) in LUAD remains unclear. In our study, comprehensive bioinformatics analysis was performed to construct a prognostic gene model and ceRNA network. The correlations between PRGs and tumour-immune infiltration, tumour mutation burden, and microsatellite instability were evaluated using Pearson’s correlation analysis. A total of 23 PRGs were upregulated or downregulated in LUAD. The genetic mutation variation landscape of PRG in LUAD was also summarised. Functional enrichment analysis revealed that these 33 PRGs were mainly involved in pyroptosis, the NOD-like receptor signalling pathway, and the Toll-like receptor signalling pathway. Prognosis analysis indicated a poor survival rate in LUAD patients with low expression of NLRP7, NLRP1, NLRP2, and NOD1 and high CASP6 expression. A prognostic PRG model constructed using the above five prognostic genes could predict the overall survival of LUAD patients with medium-to-high accuracy. Significant correlation was observed between prognostic PRGs and immune-cell infiltration, tumour mutation burden, and microsatellite instability. A ceRNA network was constructed to identify a lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis in LUAD. In conclusion, we performed a comprehensive bioinformatics analysis and identified a prognostic PRG signature containing five genes (NLRP7, NLRP1, NLRP2, NOD1, and CASP6) for LUAD patients. Our results also identified a lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis, which may also play an important role in the progression of LUAD. Further study needs to be conducted to verify this result.

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