LIN28B and Let-7 in Diffuse Midline Glioma: A Review.

LIN28B and Let-7 in Diffuse Midline Glioma: A Review.
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DOI:
10.3390/cancers15123241
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发表时间:
2023-06-19
期刊:
影响因子:
5.2
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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弥漫性中线胶质瘤(DMG)是一种破坏性的儿童脑肿瘤,迫切需要新的治疗方式。LIN28B RNA结合蛋白在DMG中过度表达,抑制let-7 microrna家族,从而抑制过多的致癌基因。在本综述中,我们总结了不同胶质瘤亚型的lin28b - let-7癌基因轴,并建议未来针对DMG的研究,将其作为潜在的治疗脆弱性。弥漫性中线胶质瘤(DMG)是所有儿童癌症中最致命的。dmg是由组蛋白尾部突变介导的表观遗传失调和控制增殖和迁移的基因的伴侣突变驱动的。这种表观遗传和遗传景观的一个结果是LIN28B RNA结合蛋白的过度表达。在其他系统中,LIN28B已被证明可以阻止let-7 microRNA的生物发生;然而,当可用时,let-7通过阻止许多癌基因的翻译,忠实地抑制致瘤途径并诱导细胞成熟。在这里,我们回顾了目前关于LIN28A/B和let-7家族的文献,并描述了它们在胶质瘤发生中的作用。然后建议未来的研究,重点关注LIN28B在DMG中的过表达和定位机制。
Diffuse midline glioma (DMG) is a devastating pediatric brain tumor with urgent unmet need for novel treatment modalities. LIN28B RNA binding protein is overexpressed in DMG and suppresses the let-7 family of microRNAs, which in turn suppress a plethora of oncogenes. In the present review, we summarize this LIN28B–let-7–oncogene axis across glioma subtypes and advise future research specific to DMG, offering it as a potential therapeutic vulnerability. Diffuse midline glioma (DMG) is the most lethal of all childhood cancers. DMGs are driven by histone-tail-mutation-mediated epigenetic dysregulation and partner mutations in genes controlling proliferation and migration. One result of this epigenetic and genetic landscape is the overexpression of LIN28B RNA binding protein. In other systems, LIN28B has been shown to prevent let-7 microRNA biogenesis; however, let-7, when available, faithfully suppresses tumorigenic pathways and induces cellular maturation by preventing the translation of numerous oncogenes. Here, we review the current literature on LIN28A/B and the let-7 family and describe their role in gliomagenesis. Future research is then recommended, with a focus on the mechanisms of LIN28B overexpression and localization in DMG.
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