Long Non-coding RNA MALAT1/microRNA-143/VEGFA Signal Axis Modulates Vascular Endothelial Injury-Induced Intracranial Aneurysm

Background/Aims: ALT1 is a novel long non-coding RNA derived from the alternatively spliced transcript of the deleted in lymphocytic leukemia 2 (DLEU2). To date, ALT1 biological roles in human vascular endothelial cells have not been reported. Methods: ALT1 was knocked down by siRNAs. Cell proliferation was analyzed by cck-8. The existence and sequence of human ALT1 were identified by 3’ rapid amplification of cDNA ends. The interaction between lncRNA and proteins was analyzed by RNA-Protein pull down assay, RNA immunoprecipitation, and mass spectrometry analysis. Results: ALT1 was expressed in human umbilical vein endothelial cells (HUVECs). The expression of ALT1 was significantly downregulated in contact-inhibited HUVECs and in hypoxia-induced, growth-arrested HUVECs. Knocking down of ALT1 inhibited the proliferation of HUVECs by G0/G1 cell cycle arrest. We observed that angiotensin converting enzyme Ⅱ(ACE2) was a direct target gene of ALT1. Knocking-down of ALT1 or its target gene ACE2 could efficiently decrease the expression of cyclin D1 via the enhanced ubiquitination and degradation, in which HIF-1α and protein von Hippel-Lindau (pVHL) might be involved. Conclusion: The results suggested the human long non-coding RNA ALT1 is a novel regulator for cell cycle of HUVECs via ACE2 and cyclin D1 pathway.

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Long non-coding RNA HOX transcript antisense RNA (HOTAIR) suppresses the angiogenesis of human placentation by inhibiting vascular endothelial growth factor A expression

Reproduction Fertility and Development ◽

10.1071/rd18118 ◽

2019 ◽

Vol 31 (2) ◽

pp. 377 ◽

Cited By ~ 4

Author(s):

Kejia Wu ◽

Fulin Liu ◽

Wanrong Wu ◽

Yurou Chen ◽

Hanshu Wu ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Human Placenta ◽

Antisense Rna ◽

Tube Formation ◽

Luciferase Reporter ◽

Vascular Endothelial ◽

Non Coding Rna ◽

Endothelial Growth Factor ◽

Long Non Coding Rna

HOX transcript antisense RNA (HOTAIR) is a long non-coding RNA located within the Homeobox C (HOXC) gene cluster on chromosome 12. Previous studies have revealed that HOTAIR is overexpressed in many types of cancers and is associated with metastasis and poor survival rates; however, few reports have mentioned the relationship between HOTAIR and angiogenesis of the human placenta. The aim of the present study was to investigate the correlation between HOTAIR and vascular endothelial growth factor (VEGF) A in the human placenta. HOTAIR levels decreased significantly in human placenta with increasing gestational age, and were negatively correlated with VEGFA levels. Invitro assays revealed that HOTAIR overexpression suppressed the proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs); however, inhibition of HOTAIR had the opposite effects. Furthermore, VEGFA overexpression reversed the inhibitory effect of HOTAIR on the proliferation, migration, invasion and tube formation of HUVECs. In addition, overexpression of HOTAIR significantly inhibited VEGFA expression. Notably, a luciferase reporter assay found that HOTAIR inhibited VEGFA transcription by directly targeting the VEGFA promoter. Together, these results suggest that HOTAIR plays an important role in suppressing angiogenesis of the human placenta by inhibiting the expression of VEGFA; thus, HOTAIR may represent a potential therapeutic target for patients with human placental vascularisation abnormalities.

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Long non-coding RNA H19 promotes corneal neovascularization by targeting microRNA-29c

Bioscience Reports ◽

10.1042/bsr20182394 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 7

Author(s):

Baoqi Sun ◽

Yiheng Ding ◽

Xin Jin ◽

Shuo Xu ◽

Hong Zhang

Keyword(s):

Growth Factor ◽

Umbilical Vein ◽

Corneal Neovascularization ◽

Tube Formation ◽

Vascular Endothelial ◽

Non Coding Rna ◽

Umbilical Vein Endothelial Cells ◽

Endothelial Growth Factor ◽

Long Non Coding Rna

AbstractLong non-coding RNA (lncRNA) H19 has been implicated in tumor angiogenesis. However, whether H19 regulates the progression of corneal neovascularization (CNV) is unclear. The present study aimed to determine the function of H19 in CNV and its possible molecular mechanism. Here, we found that the H19 levels were remarkably increased in vascularized corneas and basic fibroblast growth factor (bFGF)-treated human umbilical vein endothelial cells (HUVECs). In vitro, H19 up-regulation promoted proliferation, migration, tube formation and vascular endothelial growth factor A (VEGFA) expression in HUVECs, and it was found to down-regulate microRNA-29c (miR-29c) expression. Bioinformatics analysis revealed that H19 mediated the above effects by binding directly to miR-29c. In addition, miR-29c expression was markedly reduced in vascularized corneas and its expression also decreased in bFGF-treated HUVECs in vitro. MiR-29c targeted the 3′ untranslated region (3′-UTR) of VEGFA and decreased its expression. These data suggest that H19 can enhance CNV progression by inhibiting miR-29c, which negatively regulates VEGFA. This novel regulatory axis may serve as a potential therapeutic target for CNV.

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Long Non-Coding RNA Modulation of VEGF-A during Hypoxia

Non-Coding RNA ◽

10.3390/ncrna4040034 ◽

2018 ◽

Vol 4 (4) ◽

pp. 34 ◽

Cited By ~ 2

Author(s):

Tiina Nieminen ◽

Tristan Scott ◽

Feng-Mao Lin ◽

Zhen Chen ◽

Seppo Yla-Herttuala ◽

...

Keyword(s):

Dependent Manner ◽

Vascular Endothelial ◽

Non Coding Rna ◽

Promising Therapeutic Target ◽

Antisense Lncrnas ◽

Ischemic Diseases ◽

And Function ◽

Endothelial Growth Factor ◽

Long Non Coding Rna ◽

Role And Function

The role and function of long non-coding RNAs (lncRNAs) in modulating gene expression is becoming apparent. Vascular endothelial growth factor A (VEGF-A) is a key regulator of blood vessel formation and maintenance making it a promising therapeutic target for activation in ischemic diseases. In this study, we uncover a functional role for two antisense VEGF-A lncRNAs, RP1-261G23.7 and EST AV731492, in transcriptional regulation of VEGF-A during hypoxia. We find here that both lncRNAs are polyadenylated, concordantly upregulated with VEGF-A, localize to the VEGF-A promoter and upstream elements in a hypoxia dependent manner either as a single-stranded RNA or DNA bound RNA, and are associated with enhancer marks H3K27ac and H3K9ac. Collectively, these data suggest that VEGF-A antisense lncRNAs, RP1-261G23.7 and EST AV731492, function as VEGF-A promoter enhancer-like elements, possibly by acting as a local scaffolding for proteins and also small RNAs to tether.

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