Center for Cell and Gene Therapy, Stem Cell and Regenerative Medicine Center, Department of Molecular and Cellular Biology, Department of Neuroscience, Translational Biology and Molecular Medicine Program, Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas.
Cancer Res. 2023 May 15;83(10):1563-1572. doi: 10.1158/0008-5472.CAN-23-0296.
Extensive studies have focused on the misregulation of individual miRNAs in cancer. More recently, mutations in the miRNA biogenesis and processing machinery have been implicated in several malignancies. Such mutations can lead to global miRNA misregulation, which may promote many of the well-known hallmarks of cancer. Interestingly, recent evidence also suggests that oncogenic Kristen rat sarcoma viral oncogene homolog (KRAS) mutations act in part by modulating the activity of members of the miRNA regulatory pathway. Here, we highlight the vital role mutations in the miRNA core machinery play in promoting malignant transformation. Furthermore, we discuss how mutant KRAS can simultaneously impact multiple steps of miRNA processing and function to promote tumorigenesis. Although the ability of KRAS to hijack the miRNA regulatory pathway adds a layer of complexity to its oncogenic nature, it also provides a potential therapeutic avenue that has yet to be exploited in the clinic. Moreover, concurrent targeting of mutant KRAS and members of the miRNA core machinery represents a potential strategy for treating cancer.
大量研究集中在癌症中单个 miRNA 的失调上。最近,miRNA 生物发生和加工机制中的突变与几种恶性肿瘤有关。这种突变可能导致全局 miRNA 失调,这可能促进许多众所周知的癌症特征。有趣的是,最近的证据还表明致癌性 Kirsten 大鼠肉瘤病毒致癌基因同源物 (KRAS) 突变部分通过调节 miRNA 调节途径的成员的活性起作用。在这里,我们强调了 miRNA 核心机制中的突变在促进恶性转化中的重要作用。此外,我们讨论了突变型 KRAS 如何同时影响 miRNA 加工和功能的多个步骤,以促进肿瘤发生。虽然 KRAS 劫持 miRNA 调节途径的能力增加了其致癌性质的复杂性,但它也提供了一个尚未在临床上开发的潜在治疗途径。此外,同时靶向突变型 KRAS 和 miRNA 核心机制成员代表了治疗癌症的一种潜在策略。