Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115, USA.
Harvard College, Cambridge, MA 02138, USA.
Genes (Basel). 2021 Aug 24;12(9):1301. doi: 10.3390/genes12091301.
SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene family. It plays important roles in the maintenance of self-renewal and pluripotency of embryonic stem cells, and its expression is repressed in most adult organs. SALL4 re-expression has been observed in different types of human cancers, and dysregulation of SALL4 contributes to the pathogenesis, metastasis, and even drug resistance of multiple cancer types. Surprisingly, little is known regarding how SALL4 expression is controlled, but recently microRNAs (miRNAs) have emerged as important regulators of SALL4. Due to the ability of regulating targets differentially in specific tissues, and recent advances in systemic and organ specific miRNA delivery mechanisms, miRNAs have emerged as promising therapeutic targets for cancer treatment. In this review, we summarize current knowledge of the interaction between SALL4 and miRNAs in mammalian development and cancer, paying particular attention to the emerging roles of the Let-7/Lin28 axis. In addition, we discuss the therapeutic prospects of targeting SALL4 using miRNA-based strategies, with a focus on the Let-7/LIN28 axis.
SALL4 是一种锌指转录因子,属于 spalt-like(SALL)基因家族。它在维持胚胎干细胞的自我更新和多能性方面发挥着重要作用,其表达在大多数成人器官中受到抑制。SALL4 的重新表达已在不同类型的人类癌症中观察到,SALL4 的失调导致多种癌症的发病机制、转移甚至耐药性。令人惊讶的是,人们对 SALL4 表达的调控知之甚少,但最近 microRNAs(miRNAs)已成为 SALL4 的重要调控因子。由于能够在特定组织中差异调控靶标,以及系统和器官特异性 miRNA 传递机制的最新进展,miRNAs 已成为癌症治疗有前途的治疗靶点。在这篇综述中,我们总结了 SALL4 和 miRNA 在哺乳动物发育和癌症中的相互作用的最新知识,特别关注 Let-7/Lin28 轴的新兴作用。此外,我们讨论了使用 miRNA 为基础的策略靶向 SALL4 的治疗前景,重点是 Let-7/LIN28 轴。