Long noncoding RNA LINC00305 promotes inflammation by activating the AHRR-NF-k B pathway in human monocytes

Dan Dan Zhang, Wen Tian Wang, Jian Xiong, Xue Min Xie, Shen Shen Cui, Zhi Guo Zhao, Mulin Jun Li, Zhu Qin Zhang, De Long Hao, Xiang Zhao, Yong Jun Li, Junwen Wang, Hou Zao Chen, Xiang Lv, De Pei Liu

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27 Scopus citations

Abstract

Accumulating data from genome-wide association studies (GWAS) have provided a collection of novel candidate genes associated with complex diseases, such as atherosclerosis. We identified an atherosclerosis-associated single-nucleotide polymorphism (SNP) located in the intron of the long noncoding RNA (lncRNA) LINC00305 by searching the GWAS database. Although the function of LINC00305 is unknown, we found that LINC00305 expression is enriched in atherosclerotic plaques and monocytes. Overexpression of LINC00305 promoted the expression of inflammation-associated genes in THP-1 cells and reduced the expression of contractile markers in co-cultured human aortic smooth muscle cells (HASMCs). We showed that overexpression of LINC00305 activated nuclear factor-kappa beta (NF-k B) and that inhibition of NF-k B abolished LINC00305-mediated activation of cytokine expression. Mechanistically, LINC00305 interacted with lipocalin-1 interacting membrane receptor (LIMR), enhanced the interaction of LIMR and aryl-hydrocarbon receptor repressor (AHRR), and promoted protein expression as well as nuclear localization of AHRR. Moreover, LINC00305 activated NF-k B exclusively in the presence of LIMR and AHRR. In light of these findings, we propose that LINC00305 promotes monocyte inflammation by facilitating LIMR and AHRR cooperation and the AHRR activation, which eventually activates NF-k B, thereby inducing HASMC phenotype switching.

Original languageEnglish (US)
Article number46204
JournalScientific reports
Volume7
DOIs
StatePublished - Apr 10 2017

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    Zhang, D. D., Wang, W. T., Xiong, J., Xie, X. M., Cui, S. S., Zhao, Z. G., Li, M. J., Zhang, Z. Q., Hao, D. L., Zhao, X., Li, Y. J., Wang, J., Chen, H. Z., Lv, X., & Liu, D. P. (2017). Long noncoding RNA LINC00305 promotes inflammation by activating the AHRR-NF-k B pathway in human monocytes. Scientific reports, 7, [46204]. https://doi.org/10.1038/srep46204