Hara Tomoaki, Meng Sikun, Arao Yasuko, Saito Yoshiko, Inoue Kana, Rennie Sarah, Ofusa Ken, Doki Yuichiro, Eguchi Hidetoshi, Kitagawa Toru, Ishii Hideshi
Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Osaka, Japan.
Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Cancer Sci. 2025 Jan;116(1):8-20. doi: 10.1111/cas.16380. Epub 2024 Nov 1.
Elucidating the mechanisms underlying cancer development and proliferation is important for the development of therapeutic methods for the complete cure of cancer. In particular, the identification of diagnostic markers for early detection and new therapeutic strategies for refractory gastrointestinal cancers are needed. Various abnormal phenomena occur in cancer cells, such as functional changes of proteins, led by genomic mutations, and changes in gene expression due to dysregulation of epigenetic regulation. This is no exception for noncoding RNA (ncRNA), which do not encode proteins. Recent reports have revealed that microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA) are deeply involved in cancer progression. These ncRNAs have attracted attention as gene expression regulatory molecules. Recent advances in technology have made it possible not only to read DNA and RNA sequences but also to study the modification state of each base. In particular, comprehensive analysis of N6-methyladenosine (mA) has been performed by many research groups, with multiple studies reporting that mA modifications of specific genes are associated with cancer progression. Based on the above, this review examines how ncRNA modifications are related to cancer progression in gastrointestinal cancers such as colorectal and pancreatic cancer. We also discuss enzyme inhibitors that have been reported to have drug discovery potential targeting mA modifications. By utilizing the new perspective of ncRNA modification, we may be able to accumulate knowledge on the molecular biology of cancer and contribute to human health through diagnosis and treatment.
阐明癌症发生和增殖的潜在机制对于开发彻底治愈癌症的治疗方法至关重要。特别是，需要鉴定用于早期检测的诊断标志物以及针对难治性胃肠道癌症的新治疗策略。癌细胞中会出现各种异常现象，例如由基因组突变导致的蛋白质功能变化，以及由于表观遗传调控失调引起的基因表达变化。对于不编码蛋白质的非编码RNA（ncRNA）来说也是如此。最近的报告显示，微小RNA（miRNA）、长链非编码RNA（lncRNA）和环状RNA（circRNA）都与癌症进展密切相关。这些ncRNA作为基因表达调控分子受到了关注。技术上的最新进展不仅使读取DNA和RNA序列成为可能，还能研究每个碱基的修饰状态。特别是，许多研究小组对N6-甲基腺苷（m⁶A）进行了全面分析，多项研究报告称特定基因的m⁶A修饰与癌症进展有关。基于上述情况，本综述探讨了ncRNA修饰与结直肠癌和胰腺癌等胃肠道癌症的癌症进展之间的关系。我们还讨论了据报道具有针对m⁶A修饰的药物发现潜力的酶抑制剂。通过利用ncRNA修饰的新视角，我们或许能够积累癌症分子生物学方面的知识，并通过诊断和治疗为人类健康做出贡献。
