Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells Through miR-195

Abstract

Background/Aims: Recent studies have suggested that several lncRNAs contribute to the angiogenic function of endothelial cells. Herein, we set out to reveal whether lncRNA UCA1 has functions in endothelial angiogenesis. Methods: The expression levels of lncRNA UCA1, miR-195 and CCND1 in human microvascular endothelial HMEC-1 cells were altered by transfection. Subsequently, cell viability, migration, tube formation and apoptosis of HMEC-1 cells were respectively assessed. The cross-talk between lncRNA UCA1, miR-195, CCND1, and MEK/ERK and mTOR signaling pathways were investigated by performing qRT-PCR and Western blotting. Results: Silence of lncRNA UCA1 repressed HMEC-1 cells viability, migration, tube formation, and induced apoptosis. Meanwhile, silence of lncRNA UCA1 significantly up-regulated miR-195 expression. These alterations induced by lncRNA UCA1 were further enhanced by miR-195 overexpression, while were attenuated by miR-195 suppression. Moreover, silence of lncRNA UCA1 deactivated MEK/ERK and mTOR signaling pathways via a miR-195-dependent regulation. And the deactivation of MEK/ERK and mTOR signaling pathways led to a down-regulation of CCND1. Conclusion: This study demonstrates that silence of lncRNA UCA1 largely represses microvascular endothelial cells growth and tube formation. Silence of lncRNA UCA1 exerts its function possibly via up-regulation of miR-195, which in turn inactivates MEK/ERK and mTOR signaling pathways, and ultimately represses CCND1 expression.

Downregulated lncRNA UCA1 acts as ceRNA to adsorb microRNA-498 to repress proliferation, invasion and epithelial mesenchymal transition of esophageal cancer cells by decreasing ZEB2 expression

“…It fitted well with the previously defined role that UCA1-overexpressing SHG44 cells performed a significant reduction in miR-204-5p in comparison with the vector control cells [27]. The observation results were consistent that the functional impacts of lncRNA UCA1 silence on HMEC-1 cells growth, migration and tube formation were attenuated when miR-195 was suppressed [28]. Our findings suggested that promotion miR-498 expression decreased ZEB2 expression in EC.…”

A Novel Scaffold-Based Hybrid Multicellular Model for Pancreatic Ductal Adenocarcinoma—Toward a Better Mimicry of the in vivo Tumor Microenvironment

“…Due to the abundance of stellate cells, the growth of HMEC endothelial cells was reduced within this system, and a relatively low number CD-31 positive cells were observed (Figure 7). Overall, we did not observe any sprouting and vessel formation within our co-culture, which may suggest a need for more specialized media containing growth factors promoting angiogenesis like VEGF, or those found in Matrigel, to promote structured angiogenesis (Gerhardt et al, 2003;Son et al, 2006;Eichmann and Simons, 2012;Siemerink et al, 2012;Yin et al, 2018). It should be highlighted that although we observed some degree of cellular aging from day 28 (4 weeks) onward, both cell types (HMEC and PS-1) were present within our COL-coated PU cuboid scaffold compartment for 35 days (Figure 7), which is significantly longer than currently reported co-cultures of stellate cells and endothelial cells (Di Maggio et al, 2016).…”

Definition and review on a category of long non-coding RNA: Atherosclerosis-associated circulating lncRNA (ASCLncRNA)

“…For example, it could protect cardiomyocytes from H 2 O 2 -induced apoptosis by targeting miR-1( Yan et al, 2016 ). In cardiovascular diseases, Yin et al found that the silencing of UCA1 could induce apoptosis and repress the viability, migration, tube formation of human microvascular ECs ( Yin, Fu & Sun, 2018 ). Hu et al found that the knockdown of UCA1 in THP-1 cells could repress the formation of foam cells and restrain the total cholesterol and triglyceride levels via sponging miR-206 ( Hu et al, 2019b ).…”