ABSTRACT
The long noncoding RNA HOXA-AS3 has recently been reported to act as a critical regulator in inflammation-linked lung adenocarcinoma. However, the roles of HOXA-AS3 in endothelium inflammation and related vascular disorders remain poorly defined. In the current study, we identified HOXA-AS3 to be a critical activator to promote NF-κB-mediated endothelium inflammation. HOXA-AS3, a chromatin-associated regulator which colocalizes with NF-κB at specific gene promoters, was found to interact with NF-κB and positively regulate its activity through control of the expression of the NF-κB inhibitor protein IκBα and the acetylation status at the K310 site of p65. More importantly, clinicopathological analysis showed that HOXA-AS3 expression has a significant positive correlation with atherosclerosis. Thus, we conclude that HOXA-AS3 may serve as a crucial biomarker for the clinical diagnosis of atherosclerosis, as well as a promising therapeutic target for the treatment of multiple inflammatory vascular diseases. In addition, this study suggests the functional importance of HOXA-AS3 in the regulation of inflammatory disorders.
ACKNOWLEDGMENTS
This work was supported by grants from the National Natural Science Foundation of China (grants 81500354, 31502045, and 81600987) and the Shenzhen Science Foundation (grants JCYJ20160308104109234 and KQJSCX20170728150303243).
Yizhou Jiang and Xinxing Zhu conceived and designed the project. Xinxing Zhu, Duchu Chen, Yanli Liu, and Jinjin Yu performed most of the experiments. Genshen Zhong helped to analyze the clinicopathological samples. Liang Qiao, Yize Wang, and Xinqi Zhong contributed to data collections. Shuibin Lin and Demeng Chen performed statistical analysis. Xinxing Zhu wrote the draft of the manuscript. Xifeng Lu and Jieqi Wen helped revise the manuscript. All authors contributed to discussions.
We declare that there is no conflict of interest.