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<p>RNA G-quadruplexes (rG4s) are RNA secondary structures formed by the folding of guanine-rich sequences. As emerging post-transcriptional regulatory elements, rG4s play crucial roles at multiple levels of gene expression regulation. In recent years, the pivotal roles of rG4s in cancer initiation and progression have gained increasing attention. In tumor biology, the structural stability and dynamic folding properties of rG4s directly influence the expression of key oncogenes, thereby regulating malignant phenotypes such as tumor cell proliferation, invasion, metastasis, and drug resistance. We summarize the diverse mechanisms by which rG4s regulate cancer-related genes and review recent advances in their roles in translational control, alternative splicing, mRNA stability, and noncoding RNA functions. Furthermore, we discuss emerging rG4-targeting technologies and their potential to specifically modulate rG4-mediated gene expression in tumors. Our aim is to provide new insights into the mechanisms of rG4 function in cancer and to offer novel strategies for developing targeted cancer therapies directed at specific rG4-containing transcripts. </p> Graphical Abstract <p></p>

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RNA G-quadruplexes in oncogene regulation and as emerging targets for cancer therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月11日

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  • Zi-yan Liu,
  • Xiao-yan Wang,
  • Dan-dan Gong,
  • Xuan Tang,
  • Chang-feng Man,
  • Shi-qi Zhang,
  • Yu Fan

摘要

RNA G-quadruplexes (rG4s) are RNA secondary structures formed by the folding of guanine-rich sequences. As emerging post-transcriptional regulatory elements, rG4s play crucial roles at multiple levels of gene expression regulation. In recent years, the pivotal roles of rG4s in cancer initiation and progression have gained increasing attention. In tumor biology, the structural stability and dynamic folding properties of rG4s directly influence the expression of key oncogenes, thereby regulating malignant phenotypes such as tumor cell proliferation, invasion, metastasis, and drug resistance. We summarize the diverse mechanisms by which rG4s regulate cancer-related genes and review recent advances in their roles in translational control, alternative splicing, mRNA stability, and noncoding RNA functions. Furthermore, we discuss emerging rG4-targeting technologies and their potential to specifically modulate rG4-mediated gene expression in tumors. Our aim is to provide new insights into the mechanisms of rG4 function in cancer and to offer novel strategies for developing targeted cancer therapies directed at specific rG4-containing transcripts.

Graphical Abstract