Dataset Information

H19 Promotes Osteoblastic Transition by Acting as ceRNA of miR-140-5p in Vascular Smooth Muscle Cells.

ABSTRACT: Arterial medial calcification is a common disease in patients with type 2 diabetes, end-stage renal disease and hypertension, resulting in high incidence and mortality of cardiovascular event. H19 has been demonstrated to be involved in cardiovascular diseases like aortic valve diseases. However, role of H19 in arterial medial calcification remains largely unknown. We identified that H19 was upregulated in ß-glycerophosphate (β-GP) induced vascular smooth muscle cells (VSMCs), a cellular calcification model in vitro. Overexpression of H19 potentiated while knockdown of H19 inhibited osteogenic differentiation of VSMCs, as demonstrated by changes of osteogenic genes Runx2 and ALP as well as ALP activity. Notably, H19 interacted with miR-140-5p directly, as demonstrated by luciferase report system and RIP analysis. Mechanistically, miR-140-5p attenuated osteoblastic differentiation of VSMCs by targeting Satb2 and overexpression of miR-140-5p blocked H19 induced elevation of Satb2 as well as the promotion of osteoblastic differentiation of VSMCs. Interestingly, over-expression of Satb2 induced phosphorylation of ERK1/2 and p38MAPK. In conclusion, H19 promotes VSMC calcification by acting as competing endogenous RNA of miR-140-5p and at least partially by activating Satb2-induced ERK1/2 and p38MAPK signaling.

SUBMITTER: Xu F

PROVIDER: S-EPMC8859097 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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H19 Promotes Osteoblastic Transition by Acting as ceRNA of miR-140-5p in Vascular Smooth Muscle Cells.

Xu Feng F Zhong Jia-Yu JY Guo Bei B Lin Xiao X Wu Feng F Li Fu-Xing-Zi FX Shan Su-Kang SK Zheng Ming-Hui MH Wang Yi Y Xu Qiu-Shuang QS Lei Li-Min LM Tan Chang-Ming CM Liao Xiao-Bo XB Yuan Ling-Qing LQ

Frontiers in cell and developmental biology 20220207

Arterial medial calcification is a common disease in patients with type 2 diabetes, end-stage renal disease and hypertension, resulting in high incidence and mortality of cardiovascular event. H19 has been demonstrated to be involved in cardiovascular diseases like aortic valve diseases. However, role of H19 in arterial medial calcification remains largely unknown. We identified that H19 was upregulated in <i>ß</i>-glycerophosphate (<i>β</i>-GP) induced vascular smooth muscle cells (VSMCs), a ce ...[more]

PMID: 35198556

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Project description:BackgroundCompeting endogenous RNA (ceRNA) networks play important roles in the mechanism and development of a variety of diseases. This study aimed to construct a ceRNA network of hypertrophic cardiomyopathy (HCM).MethodsWe searched the Gene Expression Omnibus (GEO) database and then analyzed the RNAs of 353 samples to explore differentially expressed lncRNAs (DELs), microRNAs (miRNAs; DEMs), and messenger RNAs (DEmRNAs) during the progression of HCM. Weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and transcription factor (TF) prediction of miRNAs were also performed, and the GO terms, KEGG pathway terms, protein-protein interaction (PPI) network, and Pearson correlation network of the DEGs were visualized with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and through Pearson analysis. In addition, a ceRNA network related to HCM was constructed on the basis of the DELs, DEMs, and DEs. Finally, the function of the ceRNA network was explored via GO and KEGG enrichment analyses.ResultsThrough our analysis, 93 DELs (77 upregulated and 16 downregulated), 163 DEMs (91 upregulated and 72 downregulated), and 432 DEGs (238 upregulated and 194 downregulated) were screened. The functional enrichment analysis results for miRNAs showed that the miRNAs were mainly related to the VEGFR signaling network and the INFr pathway and were mainly regulated by TFs such as SOX1, TEAD1, and POU2F1. Gene set enrichment analysis (GSEA), GO analysis, and KEGG enrichment analysis showed that the DEGs were enriched in the Hedgehog signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. In addition, a ceRNA network including 8 lncRNAs (e.g., LINC00324, SNHG12, and ALMS1-IT1), 7 miRNAs (e.g., hsa-miR-217, hsa-miR-184, and hsa-miR-140-5p), and 52 mRNAs (e.g., IGFBP5, TMED5, and MAGT1) was constructed. The results revealed that SNHG12, hsa-miR-140-5p, hsa-miR-217, TFRC, HDAC4, TJP1, IGFBP5, and CREB5 may form an important network involved in the pathology of HCM.ConclusionsThe novel ceRNA network that we have demonstrated will provide new research points about molecular mechanisms of HCM.

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Dataset Information

H19 Promotes Osteoblastic Transition by Acting as ceRNA of miR-140-5p in Vascular Smooth Muscle Cells.

Publications

H19 Promotes Osteoblastic Transition by Acting as ceRNA of miR-140-5p in Vascular Smooth Muscle Cells.

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