Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieHypoxic Pulmonary Arterial Hypertension
CeRNA1AC068039.4[LncRNA]
miRNAmiR-26a-5p[miRNA]
CeRNA2TRPC6[mRNA]
Tissue/Cell linepulmonary artery smooth muscle cells
SpecieHomo sapiens (human)
CitationShock. 2021 Feb 1;55(2):244-255. doi: 10.1097/SHK.0000000000001606.
Reference title
Overexpressed lncRNA AC068039.4 Contributes to Proliferation and Cell Cycle Progression of Pulmonary Artery Smooth Muscle Cells Via Sponging miR-26a-5p/TRPC6 in Hypoxic Pulmonary Arterial Hypertension.
Experimental verification
microarray;qRT-PCR;Western blot;Flow Cytometry assay;Luciferase reporter assay;
Functional description
BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a devastating and incurable disease characterized by pulmonary vascular remodeling, resulting in right heart failure and even death. Accumulated evidence has confirmed long coding RNAs (lncRNAs) are involved in hypoxia-induced pulmonary vascular remodeling in HPH. The exact mechanism of lncRNA in hypoxic pulmonary hypertension remains unclear. METHODS: Microarray analysis was applied to investigate the profiles of lncRNA expression in pulmonary artery smooth muscle cells (PASMCs) cultured under hypoxia and normoxia condition. qRT-PCR was performed for the expression of lncRNAs, miRNA, and mRNAs, western blot analysis was employed for the detection of the expression of proteins. CCK-8 and transwell chamber assay were applied for the assessment of PASMC proliferation and migration, respectively. Besides, flow cytometry was performed for assessments of cell cycle progression. The binding between AC068039.4 and miR-26a-5p, miR-26a-5p, and TRPC6 3'UTR was detected by dual luciferase reporter assay. RESULTS: A total of 1,211 lncRNAs (698 up-regulated and 513 down-regulated) were differently expressed in hypoxia-induced PASMCs. Consistent with microarray analysis, quantitative PCR verified that AC068039.4 was obviously up-regulated in hypoxia-induced PASMCs. Knocking down AC068039.4 alleviated proliferation and migration of PASMCs and regulated cell cycle progression through inhibiting cells entering the G0/G1 cell cycle phase. Further experiment indicated AC068039.4 promoted hypoxic PASMCs proliferation via sponging miR-26-5p. In addition, transient receptor potential canonical 6 (TRPC6) was confirmed to be a target gene of miR-26a-5p. CONCLUSION: In conclusion, downregulation of lncRNA AC068039.4 inhibited pulmonary vascular remodeling through AC068039.4/miR-26a-5p/TRPC6 axis, providing new therapeutic insights for the treatment of HPH.
Annotations
External Annotation for AC068039.4 |
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LncRNA-associated competing triplets and functions. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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Infer genomic variations that disturb lncRNA-associated ceRNA regulation.. |
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Provide and annotate disease or phenotype-associated variants in human long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) or their regulatory elements. |
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Providing cellular-specific lncRNA-associated ceRNA networks predicted via high-throughput analysis of single-cell genomic data. |
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Information on all annotated and predicted human genes. |
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Gene nomenclature, gene families and associated resources (genomic, proteomic, phenotypic information). |
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Genome browser for vertebrate genomes. |
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An annotated collection of all publicly available DNA sequences. |
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A wiki-based platform for community curation of human long non-coding RNAs. |
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An integrated knowledge database dedicated to non-coding RNAs. |
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An integrated database of human annotated lncRNA transcripts. |
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Comprehensive annotations of eukaryotic long non-coding RNAs. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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A comprehensive, authoritative compendium of human genes and genetic phenotypes. |
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The catalogue of somatic mutations in cancer. |
