Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu 603203, Tamil Nadu, India.
Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamil Nadu, India.
Cells. 2023 Oct 17;12(20):2467. doi: 10.3390/cells12202467.
Fusion genes are key cancer driver genes that can be used as potential drug targets in precision therapies, and they can also serve as accurate diagnostic and prognostic biomarkers. The fusion genes can cause microRNA (miRNA/miR) aberrations in many types of cancer. Nevertheless, whether fusion genes incite miRNA aberrations as one of their many critical oncogenic functionalities for driving carcinogenesis needs further investigation. Recent discoveries of miRNA genes that are present within the regions of genomic rearrangements that initiate fusion gene-based intronic miRNA dysregulation have brought the fusion genes into the limelight and revealed their unexplored potential in the field of cancer biology. Fusion gene-based 'promoter-switch' event aberrantly activate the miRNA-related upstream regulatory signals, while fusion-based coding region alterations disrupt the original miRNA coding loci. Fusion genes can potentially regulate the miRNA aberrations regardless of the protein-coding capability of the resultant fusion transcript. Studies on out-of-frame fusion and nonrecurrent fusion genes that cause miRNA dysregulation have attracted the attention of researchers on fusion genes from an oncological perspective and therefore could have potential implications in cancer therapies. This review will provide insights into the role of fusion genes and miRNAs, and their possible interrelationships in cancer.
融合基因是关键的癌症驱动基因,可作为精准治疗中的潜在药物靶点,也可作为准确的诊断和预后生物标志物。融合基因可导致多种类型癌症中的 microRNA(miRNA/miR)异常。然而,融合基因是否将 miRNA 异常作为其众多关键致癌功能之一,以驱动癌变,仍需要进一步研究。最近发现 miRNA 基因存在于引发融合基因内含子 miRNA 失调的基因组重排区域内,这将融合基因推到了聚光灯下,并揭示了它们在癌症生物学领域尚未探索的潜力。融合基因的“启动子转换”事件异常激活了与 miRNA 相关的上游调控信号,而融合基因的编码区改变则破坏了原始 miRNA 编码基因座。融合基因可能会调节 miRNA 异常,而不管融合转录本的蛋白质编码能力如何。对导致 miRNA 失调的无框融合和非重复融合基因的研究引起了从肿瘤学角度研究融合基因的研究人员的关注,因此可能对癌症治疗具有潜在意义。本文综述将深入探讨融合基因和 miRNA 的作用及其在癌症中的可能相互关系。