AUTHOR=Luo Xiaoqing , Zhang Jianye , Gao Yue , Pan Weifei , Yang Yayuan , Li Xu , Chen Lingfei , Wang Chang , Wang Yuqing TITLE=Emerging roles of i-motif in gene expression and disease treatment JOURNAL=Frontiers in Pharmacology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1136251 DOI=10.3389/fphar.2023.1136251 ISSN=1663-9812 ABSTRACT=

As non-canonical nucleic acid secondary structures consisting of cytosine-rich nucleic acids, i-motifs can form under certain conditions. Several i-motif sequences have been identified in the human genome and play important roles in biological regulatory functions. Due to their physicochemical properties, these i-motif structures have attracted attention and are new targets for drug development. Herein, we reviewed the characteristics and mechanisms of i-motifs located in gene promoters (including c-myc, Bcl-2, VEGF, and telomeres), summarized various small molecule ligands that interact with them, and the possible binding modes between ligands and i-motifs, and described their effects on gene expression. Furthermore, we discussed diseases closely associated with i-motifs. Among these, cancer is closely associated with i-motifs since i-motifs can form in some regions of most oncogenes. Finally, we introduced recent advances in the applications of i-motifs in multiple areas.