CircRNA‑0044073 is upregulated in atherosclerosis and increases the proliferation and invasion of cells by targeting miR‑107

Abstract

Circular RNAs (circRNAs) are endogenous non-coding RNAs implicated in atherosclerosis. The aim of the present study was to explore the function of circRNA-0044073 in atherosclerosis. Reverse transcription quantitative polymerase chain reaction assays were used to measure the expression levels of circRNA-0044073, microRNA (miRNA/miR)-107, janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), B-cell lymphoma 2 (Bcl-2) and v-myc avian myelocytomatosis viral oncogene homolog (c-myc) in in blood cells from patients with atherosclerosis. RNA pull-down and luciferase reporter assays were then used to determine the association between circRNA and miR expression, and miR and gene expression, respectively. Matrigel invasion assay and flow cytometry were used to analyze cell invasion and cell cycle. Western blot analysis and ELISA were used to evaluate the expression levels of proteins. It was identified that the expression of circRNA-0044073 was upregulated and the expression of miR-107 was downregulated in atherosclerotic blood cells. Overexpression of circRNA-0044073 promoted the proliferation of human vascular smooth muscle cells (HUVSMCs) and human vascular endothelial cells (HUVECs), while overexpression of miR-107 inhibited their proliferation. In addition, circRNA-0044073 suppressed the levels of miR-107 via a sponge mechanism. Lipopolysaccharide (LPS) affected the proliferation of HUVSMCs and HUVECs, and also resulted in changes in circRNA-0044073 expression levels. CircRNA-0044073 promoted the proliferation and invasion of HUVSMCs and HUVECs in spite of the opposite effect observed with LPS treatment. The JAK/STAT signaling pathway was activated in patients with atherosclerosis. CircRNA-0044073 favored the activation of the JAK/STAT signaling pathway and inflammation in HUVSMCs and HUVECs. These data indicate that circRNA-0044073 is upregulated in atherosclerosis and promotes the proliferation and invasion of cells by targeting miR-107 and activating the JAK/STAT signaling pathway, potentially offering a target for novel treatment strategies against atherosclerosis.

CircNF1-419 improves the gut microbiome structure and function in AD-like mice

“…Recently, a report demonstrated that avian leucosis virus targets circ-Vav3 and then sponges gga-miR-375 to promote epithelial-mesenchymal transition [38], indicating that a microorganism could directly influence the formation, expression and function of circRNAs, and the mysterious of circRNA is suggested in increasing numbers of studies [30,38,39]. In order to verify these, the expression level of circRNAs was examined by qRT-PCR in AD-like mice (PCR primers are listed in Table 1).…”

“…Studies have shown that in the brain, where the level of circRNA is significantly higher, some circRNAs consist mainly of portions of the multi-exon 5′ untranslated region (5′UTR), suggesting that functions of these multi-exon 5′UTR of genes and/or circRNA is new [28]. Increasing numbers of circRNAs function in the brain, including circPDE4B [29], circRNA-0044073 [30], and circHIPK3 [31], as well as in heart failure [32,33], human cancer (Josh N, et al) [34] and other diseases [35], suggesting that circRNAs are crucial functional molecules in mammals. Thus, studying the roles of circRNAs on the gut-brain axis is important.…”

CircRNAs open a new era in the study of cardiovascular disease (Review)

“…It is understood that circRNAs are involved in numerous pathological mechanisms underlying cVds, such as AS, immune response, apoptosis, cell proliferation, autophagy, cell senescence and myocardial repair (103)(104)(105)(106)(107)(108)(109). Emerging evidence has suggested that circRNAs play an important role in the occurrence and development of cVd (110).…”

“…The proliferation of cells involved in the cardiovascular system plays an important role in the development of cVds, such as hypertension, AS and restenosis (110). circRNAs serve an important role in the development of cVds (103,111). Shen et al (103) demonstrated that circRNA-0044073 is highly expressed in patients with AS.…”

Functions of Circular RNAs in Regulating Adipogenesis of Mesenchymal Stem Cells

“…Beyond that, by repressing miR-9, circSMAD2 impedes the activation of STAT3 and MEK/ERK pathways in migration and epithelial-mesenchymal transition [122]. CircRNA-0044073 promotes the proliferation of cells by sponging miR-107 and activating the JAK/STAT signaling pathway [123]. There are still many factors that regulate adipogenesis which may be the targets of circRNAs, such as miR-143 [124], miR-130 [125], miR-145 [126], miR-181a [127], and let-7 [128].…”