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Genomic G-quadruplex folding triggers a cytokine-mediated inflammatory feedback loop to aggravate inflammatory diseases

Xiaolin Wang,Shunlun Chen,Zhuoyang Zhao,Fan Chen,Yuming Huang,Xingyu Guo,Linchuan Lei,Wantao Wang,Yanxin Luo,Huichuan Yu,Jianru Wang

Published 2022 in iScience

ABSTRACT

Summary DNA G-quadruplex is a non-canonical secondary structure that could epigenetically regulate gene expression. To investigate the regulating role of G-quadruplex, we devised an integrating method to perform the algorithm profiling and genome-wide analysis for the dynamic change of genomic G-quadruplex and RNA profiles in rat nucleus pulposus cells by inducing G-quadruplex folding with multiple stabilizers. A group of genes potentially regulated by G-quadruplex and involved in the inflammation process has been identified. We found that G-quadruplex folding triggers inflammation response by upregulating inflammatory cytokines, which could promote G-quadruplex folding in a manner of positive feedback loop. Moreover, we confirmed that G-quadruplex is a marker indicating elevated inflammatory status and G-quadruplex folding facilitates the development of inflammatory diseases using in vivo intervertebral disc degeneration models. The crosstalk between G-quadruplex and inflammatory cytokines plays a vital role in regulating inflammation-derived diseases, which may provide new insights into the blocking target.

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