The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.

Objective The aim of this study is to investigate the role of quercetin on coronary atherosclerosis and further explore its possible mechanisms. Methods Hematoxylin-eosin (H&E), Immunohistochemical (IHC) and Aniline blue staining are to analyze the pathological changes of aorta cross section. Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction and PubChem are used to predict and screen the bioactive ingredients of Traditional Chinese medicine (Haunglian, Yuxingcao and Jinyinhua) for coronary atherosclerosis. Inflammatory factors and vascular protection parameters were quantitatively detected via ELISA and western blot. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2-deoxyuridine (EdU), wound healing are conducted to detect the proliferation and migration of vascular smooth muscle cells (VSMC). DisGeNET, Matascape, SWISSMODEL, cellular thermal shift assay (CETSA) and fluorescence titrimetric are used to predict the targets of quercetin. Results We found that quercetin is the effective active component of Huanglian, Yuxingcao and Jinyinhua acting on AS. Further in vivo and in vitro data revealed that quercetin improved the pathological changes of model mice and inhibited VSMC cells proliferation, migration and inflammatory response. Mechanically, we demonstrated that fibroblast growth factor 2 (FGF2) is a direct target of quercetin, and overexpression of FGF2 attenuated the anti-AS function of quercetin. Conclusion In our study, we confirmed the functional role of the quercetin-FGF2 axis in the progression of coronary atherosclerosis, which provides a latent target for coronary atherosclerosis treatment.

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