2. Academic Validation
  3. Genomic G-quadruplex folding triggers a cytokine-mediated inflammatory feedback loop to aggravate inflammatory diseases

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.
Xiaolin Wang 1 2 3,  Shunlun Chen 1 2 4,  Zhuoyang Zhao 1 2 4,  Fan Chen 4,  Yuming Huang 4,  Xingyu Guo 4,  Linchuan Lei 4,  Wantao Wang 4,  Yanxin Luo 1 2 3,  Huichuan Yu 1 2 3,  Jianru Wang 4
Affiliations

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.
PMID: 36304116 DOI: 10.1016/j.isci.2022.105312
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.

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