Institute of Biosciences and Technology, Texas A&M Health, Houston, TX 77030, USA.
University of Kentucky College of Medicine, Lexington, KY 40506, USA.
Exp Biol Med (Maywood). 2021 Oct;246(19):2082-2097. doi: 10.1177/15353702211031247. Epub 2021 Jul 25.
LINE-1 retrotransposon, the most active mobile element of the human genome, is subject to tight regulatory control. Stressful environments and disease modify the recruitment of regulatory proteins leading to unregulated activation of LINE-1. The activation of LINE-1 influences genome dynamics through altered chromatin landscapes, insertion mutations, deletions, and modulation of cellular plasticity. To date, LINE-1 retrotransposition has been linked to various cancer types and may in fact underwrite the genetic basis of various other forms of chronic human illness. The occurrence of LINE-1 polymorphisms in the human population may define inter-individual differences in susceptibility to disease. This review is written in honor of Dr Peter Stambrook, a friend and colleague who carried out highly impactful cancer research over many years of professional practice. Dr Stambrook devoted considerable energy to helping others live up to their full potential and to navigate the complexities of professional life. He was an inspirational leader, a strong advocate, a kind mentor, a vocal supporter and cheerleader, and yes, a hard critic and tough friend when needed. His passionate stand on issues, his witty sense of humor, and his love for humanity have left a huge mark in our lives. We hope that that the knowledge summarized here will advance our understanding of the role of LINE-1 in cancer biology and expedite the development of innovative cancer diagnostics and treatments in the ways that Dr Stambrook himself had so passionately envisioned.
LINE-1 反转录转座子是人类基因组中最活跃的移动元件，受到严格的调控控制。在压力环境和疾病下，调节蛋白的募集会发生改变，导致 LINE-1 的非调控激活。LINE-1 的激活通过改变染色质景观、插入突变、缺失和细胞可塑性的调节来影响基因组动态。迄今为止，LINE-1 反转录转座已与多种癌症类型相关联，实际上可能构成了各种其他形式的慢性人类疾病的遗传基础。人类群体中 LINE-1 多态性的发生可能定义了个体对疾病易感性的差异。这篇综述是为纪念彼得·斯坦布鲁克博士而写的，他是一位朋友和同事，在多年的专业实践中开展了极具影响力的癌症研究。斯坦布鲁克博士投入了大量精力帮助他人充分发挥潜力，并应对职业生涯的复杂性。他是一位鼓舞人心的领导者、坚定的倡导者、和蔼的导师、直言不讳的支持者和啦啦队长，而且在需要时，他也是一位严厉的批评者和严厉的朋友。他对问题的热情立场、诙谐的幽默感以及对人类的热爱，在我们的生活中留下了巨大的印记。我们希望这里总结的知识将增进我们对 LINE-1 在癌症生物学中的作用的理解，并以斯坦布鲁克博士本人如此热情地设想的方式加速创新癌症诊断和治疗的发展。
