Dataset Information

Long Noncoding RNA LOC100129973 Suppresses Apoptosis by Targeting miR-4707-5p and miR-4767 in Vascular Endothelial Cells.

ABSTRACT: Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are key regulators of multiple biological processes by altering gene expression at various levels. Apoptosis in vascular endothelial cells (VECs) is closely linked to numerous cardiovascular diseases, such as arteriosclerosis, thrombus formation and plaque erosion. However, studies on lncRNAs in the cardiovascular system are just beginning. And thus far, no anti-apoptosis lncRNAs have been identified in VECs. Here, we focused on the anti-apoptosis roles of lncRNAs in the serum and FGF-2 starvation-induced apoptosis of VECs. Using microarray analysis, we found a novel lncRNA LOC100129973 which acted as an apoptosis inhibitor in VECs. Through sponging miR-4707-5p and miR-4767, lncRNA LOC100129973 upregulated the expression of two apoptosis repressors gene, Apoptosis Inhibitor 5 (API5) and BCL2 like 12 (BCL2L12), and thus alleviated the serum and FGF-2 starvation-induced apoptosis in VECs. This evidence suggests that lncRNA LOC100129973 is an attractive target to improve endothelial function and for therapy of apoptosis related cardiovascular diseases.

SUBMITTER: Lu W

PROVIDER: S-EPMC4757888 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Long Noncoding RNA LOC100129973 Suppresses Apoptosis by Targeting miR-4707-5p and miR-4767 in Vascular Endothelial Cells.

Lu Wei W Huang Shu Ya SY Su Le L Zhao Bao Xiang BX Miao Jun Ying JY

Scientific reports 20160218

Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are key regulators of multiple biological processes by altering gene expression at various levels. Apoptosis in vascular endothelial cells (VECs) is closely linked to numerous cardiovascular diseases, such as arteriosclerosis, thrombus formation and plaque erosion. However, studies on lncRNAs in the cardiovascular system are just beginning. And thus far, no anti-apoptosis lncRNAs have been identified in VECs. Here, we foc ...[more]

PMID: 26887505

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Project description:BackgroundHepatocellular carcinoma (HCC) is the major histological type of liver cancer with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNA) has been proved to be associated with various cancer types, while its regulation in HCC is largely unknown.MethodsTo figure out the specific role of lncRNA EPB41L4A-AS2 in HCC. Fluorescence in situ hybridization (FISH) was first used to determine the cellular sublocalization of EPB41L4A-AS2 to determine its primary mode of action. QRT-PCR, Western blot and hematoxylin-eosin staining were then used to measure the expression of genes in cells and tissues. Cell proliferation and invasion assays were performed to determine the effects of EPB41L4A-AS2, miR-301a-5p and FOXL1 on the malignant phenotype of tumor cells. With luciferase reporter assay, the direct interaction between target genes were further confirmed for research on molecular mechanism. Finally, the mice hepatocarcinoma model was also established to disclose the tumor suppressor effects of EPB41L4A-AS2 in vivo.ResultsHere, we have identified a novel lncRNA EPB41L4A-AS2, which is significantly downregulated both in HCC cells and tissues, and plays a negative regulatory role in HCC proliferation and invasion. Mechanistically, cytoplasmic lncRNA EPB41L4A-AS2 functions as an efficient miR-301a-5p sponge, thereby release the expression inhibition of forkhead box L1 (FOXL1). Indeed, lncRNA EPB41L4A-AS2 inhibits proliferation and migration by upregulating FOXL1 expression and FOXL1 was confirmed as a direct target of miR-301a-5p. MiR-301a-5p shows an inverse correlation with EPB41L4A-AS2 expression and was verified as a direct target of EPB41L4A-AS2 as well. Correspondingly, FOXL1 and miR-301a-5p show opposite biological effects in cell proliferation and migration. Moreover, miR-301a-5p overexpression rescued the EPB41L4A-AS2 upregulation induced depression in proliferation, migration and invasion of HCC cells, as well as promotion effect on FOXL1 expression. Also, in vivo experiments proved that EPB41L4A-AS2 suppress tumor growth and extrahepatic metastasis (lung) via the miR-301a-5p-FOXL1 axis.ConclusionsTaken together, this research revealed a concrete mechanism of lncRNA EPB41L4A-AS2 in HCC, which may serve as a potential biomarkers and novel therapeutic targets for further clinical application.

Dataset Information

Long Noncoding RNA LOC100129973 Suppresses Apoptosis by Targeting miR-4707-5p and miR-4767 in Vascular Endothelial Cells.

Publications

Long Noncoding RNA LOC100129973 Suppresses Apoptosis by Targeting miR-4707-5p and miR-4767 in Vascular Endothelial Cells.

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