Han Yangyang, Sun Jingqi, Yao Minghui, Miao Liying, Li Mengjia
Department of Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China.
Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi, 830017, China.
Cell Commun Signal. 2025 May 30;23(1):254. doi: 10.1186/s12964-025-02254-4.
Enhancers, as distal cis-regulatory elements in the genome, have a pivotal influence on orchestrating precise gene expression. Enhancer RNAs (eRNAs), transcribed from active enhancer regions, are increasingly recognized as key regulators of transcription. N6-methyladenosine (m6A), the most plentiful internal modification in eukaryotic mRNAs, has garnered significant research interest in recent years. With advancements in high-throughput sequencing technologies, it has been established that m6A modifications are also present on eRNAs. An accumulative body of evidence demonstrates that aberrant enhancers, eRNAs, and m6A modifications are intimately connected with carcinoma onset, progression, invasion, metastasis, treatment response, drug resistance, and prognosis. However, the underlying molecular mechanisms governing m6A modification of eRNAs in cancer remain elusive. Here, we review and synthesize current understanding of the regulatory roles of enhancers, eRNAs, and m6A modifications in cancer. Furthermore, we investigate the possible roles of eRNAs m6A modification in tumorigenesis based on existing literature, offering novel perspectives and directions for future research on epigenetic regulatory mechanisms in cancer cells.
增强子作为基因组中的远端顺式调控元件，对精确协调基因表达具有关键影响。从活跃增强子区域转录而来的增强子RNA（eRNA），日益被认为是转录的关键调节因子。N6-甲基腺苷（m6A）是真核生物mRNA中最丰富的内部修饰，近年来已引起了广泛的研究关注。随着高通量测序技术的进步，已证实eRNA上也存在m6A修饰。越来越多的证据表明，异常的增强子、eRNA和m6A修饰与癌症的发生、发展、侵袭、转移、治疗反应、耐药性及预后密切相关。然而，癌症中eRNA的m6A修饰的潜在分子机制仍不清楚。在此，我们综述并综合了目前对增强子、eRNA和m6A修饰在癌症中的调控作用的理解。此外，我们基于现有文献研究了eRNA的m6A修饰在肿瘤发生中的可能作用，为未来癌细胞表观遗传调控机制的研究提供了新的视角和方向。
