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

doi:10.1016/j.isci.2022.105312

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

iScience. 2022 Oct 9;25(11):105312. doi: 10.1016/j.isci.2022.105312. eCollection 2022 Nov 18.

Authors

Xiaolin Wang^{1

2

3}, Shunlun Chen^{1

2

4}, Zhuoyang Zhao^{1

2

4}, Fan Chen⁴, Yuming Huang⁴, Xingyu Guo⁴, Linchuan Lei⁴, Wantao Wang⁴, Yanxin Luo^{1

2

3}, Huichuan Yu^{1

2

3}, Jianru Wang⁴

Affiliations

¹ Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
² Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China.
³ Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
⁴ Department of Spine Surgery, Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

Abstract

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.

Keywords: Biological sciences; immunology; molecular biology; molecular mechanism of gene regulation; orthopedics.