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

CircRNA‑0044073 在动脉粥样硬化中上调,并通过靶向 miR‑107 增加细胞的增殖和侵袭

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作者:Lin Shen, Yanyan Hu, Jianwei Lou, Sen Yin, Weiling Wang, Yuanyan Wang, Yong Xia, Wei Wu

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.

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