Chen Yi-Ling, Pascuzzi Nicholas, Ruiz Alejandro, Chen Kuan-Hui Ethan
Department of Electronic Engineering, National Kaohsiung University of Science and Technology, Kaohsiung 80778, Taiwan.
Department of Biological Sciences; Texas Tech University, Lubbock, TX 79409, USA.
Onco (Basel). 2025 Mar;5(1). doi: 10.3390/onco5010007. Epub 2025 Feb 8.
Mirtrons represent a new subclass of microRNAs (miRNAs) that are processed through non-canonical biogenesis pathways. Unlike canonical miRNAs, which require Drosha-mediated cleavage, mirtrons are generated via the splicing of short intronic sequences, bypassing Drosha entirely. While mirtrons are found across a variety of organisms, their conservation between species is relatively low. This evolutionary divergence has resulted in mirtrons acquiring species-specific regulatory functions. In humans, mirtrons remain an understudied group of regulatory RNAs. However, emerging evidence highlights their critical roles in cancer biology. These small RNAs influence a range of oncogenic processes, including tumor initiation, progression, metastasis, and resistance to therapy. By directly regulating the expression of oncogenes and tumor suppressor genes, mirtrons serve as key molecular mediators within cellular signaling pathways. What sets mirtrons apart from canonical miRNAs is their unique mode of biogenesis and structural attributes, which reveal alternative regulatory mechanisms that could be exploited in cancer biology. Recent advances in understanding their functions suggest that mirtrons hold significant potential as biomarkers for cancer diagnosis and prognosis. Additionally, their role as modulators of cancer pathways positions them as promising therapeutic targets in precision oncology. This review delves into the growing body of research on mirtrons, focusing on their biogenesis, biological roles, and implications in cancer. By emphasizing their distinct features and clinical relevance, it aims to provide a comprehensive perspective on the potential applications of mirtrons in advancing cancer diagnostics and therapeutics.
微小内含子源RNA(mirtrons)是一类新的微小RNA(miRNA)亚类,通过非经典生物合成途径加工而成。与需要Drosha介导切割的经典miRNA不同,mirtrons是通过短内含子序列的剪接产生的,完全绕过了Drosha。虽然在多种生物体中都发现了mirtrons,但它们在物种间的保守性相对较低。这种进化上的差异导致mirtrons获得了物种特异性的调控功能。在人类中,mirtrons仍然是一组研究较少的调控RNA。然而,新出现的证据凸显了它们在癌症生物学中的关键作用。这些小RNA影响一系列致癌过程,包括肿瘤起始、进展、转移和对治疗的抗性。通过直接调控癌基因和肿瘤抑制基因的表达,mirtrons在细胞信号通路中充当关键的分子介质。mirtrons与经典miRNA的不同之处在于其独特的生物合成模式和结构特性,这揭示了可在癌症生物学中加以利用的替代调控机制。在理解其功能方面的最新进展表明,mirtrons作为癌症诊断和预后生物标志物具有巨大潜力。此外,它们作为癌症通路调节剂的作用使其成为精准肿瘤学中很有前景的治疗靶点。这篇综述深入探讨了关于mirtrons的越来越多的研究,重点关注它们的生物合成、生物学作用以及在癌症中的意义。通过强调它们的独特特征和临床相关性,旨在全面阐述mirtrons在推进癌症诊断和治疗方面的潜在应用。