期刊
ATHEROSCLEROSIS
卷 281, 期 -, 页码 38-46出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2018.12.012
关键词
HOXA-AS2; NF-kappa B; Negative feedback; Endothelium inflammation
资金
- National Natural Science Foundation of China [81771226, 31502045]
- Henan Province Foundation [162300410214, 19IRTSTHN003]
- Xinxiang City Foundation [CXRC16003, ZD17008]
- Xinxiang Medical University Foundation [2016PN-KFKT-03, 20172DCG-03]
Background and aims: Endothelium inflammation, which can lead to endothelial activation and dysfunction, is widely accepted as the major event in multiple vascular disorders. The lncRNA HOXA-AS2 was previously reported to be involved in multiple inflammation-linked cancers. However, the role of HOXA-AS2 in endothelium inflammation is poorly understood. This study aims to determine the regulatory role of HOXA-AS2 in endothelium inflammation and related vascular diseases. Methods: High throughput mRNA sequencing was performed to establish expression profiles after HOXA-AS2 depletion. We extracted total RNAs of human peripheral blood mononuclear cells from normal control group and experimental group with carotid artery atherosclerosis, and performed qRT-PCR to assay the correlation between HOXA-AS2 expression and inflammatory vascular diseases. Results: Inhibition of HOXA-AS2 can induce the activation of NF-kappa B signaling and subsequent inflammatory response. More importantly, HOXA-AS2 is inversely found to be inversely regulated by NF-kappa B in a negative feedback manner by helping recruit BRD4/P-TEFb complex to HOXA-AS2 promoter region, therefore facilitating release of the promoter-proximal paused RNA polymerase II and activating transcription elongation. Conclusions: We identify HOXA-AS2 as a critical repressor of endothelium inflammation. Moreover, this study offers us a new way to balance the NF-kappa B signaling-driven excessive endothelium inflammation by establishing a NF-kappa B/HOXA-AS2 negative feedback loop. Based on these findings, we conclude that HOXA-AS2 may serve as a crucial therapeutic target for various vascular disorders which are significantly associated with endothelium inflammation.
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