miR-27b Suppresses Endothelial Cell Proliferation and Migration by Targeting Smad7 in Kawasaki Disease

Abstract

Background/Aims: Increasing evidence indicates that microRNAs (miRNAs) play important roles in Kawasaki disease (KD). Our previous study demonstrated that hsa-miR-27b-3p (miR-27b) was up-regulated in KD serum. However, the specific role of miR-27b in KD remains unclear. We aimed to investigate that miR-27b could be a biomarker and therapeutic target for KD treatment. As well, the specific mechanism of miR-27b effecting endothelial cell functions was studied. Methods: The expression of miR-27b and Smad7 was measured by qRT-PCR. Gain-of-function strategy was used to observe the effect of miR-27b on human umbilical vein endothelial cells (HUVECs) proliferation and migration. Bioinformatics analyses were applied to predict miR-27b targets and then we verified Smad7 by a luciferase reporter assay. Western blot was performed to detect the protein expression of Smad7, PCNA, MMP9, MMP12 and TGF-β-related genes. Results: We confirmed that miR-27b was shown to be dramatically up-regulated in KD serum and KD serum-treated HUVECs and that elevated expression of miR-27b suppressed the proliferation and migration of HUVECs. Furthermore, our results verified that miR-27b mediated cell functions by affecting the TGF-β via targeting Smad7 in HUVECs. Conclusion: These results suggested that up-regulated miR-27b had a protective role in HUVECs proliferation and migration via targeting Smad7 and affecting TGF-β pathway. Therefore, miR-27b represented a potential biomarker for KD and may serve as a promising therapeutic target for KD treatment.

lncRNA CASC2 inhibits lipopolysaccharide‑induced acute lung injury via miR‑27b/TAB2 axis

“…mir-27b could modulate the expression of target genes at the posttranscriptional level (25,28,29). in the present study, we hypothesized whether mir-27b regulated the progression of ali through specific target genes.…”

miR‐27a/b is a posttranscriptional regulator of Gpr126 (Adgrg6)

“…Previous studies have established that morpholino‐based knockdown of gpr126 expression in zebrafish results in hypotrabeculation at 80 h postfertilization (hpf) . Because of its previously reported regulation of genes involved in heart development, miR‐27b was chosen as a candidate for performing in vivo experiments . Therefore, we injected zebrafish miR‐27b in single cell–stage Tg(myl7:EGFP‐Hsa.HRAS) embryos and analyzed their hearts at 80 hpf (Fig.…”

“…A detailed literature analysis further supports that miR‐27b regulates Gpr126 expression. miR‐27b and Gpr126 are both expressed during heart development and in endothelial cells, are both shear stress–regulated, and associated with cognitive impairment or intellectual disability, as well as bladder cancer . In addition, it is known that Gpr126 is expressed in the salivary gland, lung, and kidney, while miR‐27b is associated with non‐small cell lung cancer, clear cell renal cell cancer, and adenoid cystic carcinoma of the salivary glands .…”

Up-Regulated MicroRNA-27b Promotes Adipocyte Differentiation via Induction of Acyl-CoA Thioesterase 2 Expression

“…ese results therefore plainly indicate that the miR-27b-ACOT2 axis promotes lipid accumulation and adipocyte di erentiation, process which result in NAFLD pathogenesis. Several studies have shown that miR-27b regulates not only adipogenesis, but also cell proliferation, angiogenesis, and tumor development [14,15,40,41]. Nonetheless, the role of miR-27b has not been fully elucidated.…”

“…Nonetheless, the role of miR-27b has not been fully elucidated. For example, upregulated miR-27b in the serum of Kawasaki disease patients enhanced endothelial cell proliferation and migration by targeting Smad7 [40]. In contrast, down-regulated miR-27b promoted the activation of adenosine monophosphate-activated role in cancer metastasis [37].…”