Stricker Erik, Peckham-Gregory Erin C, Scheurer Michael E
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77047, USA.
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77047, USA.
Biomedicines. 2023 Mar 17;11(3):936. doi: 10.3390/biomedicines11030936.
Genomic instability and genetic mutations can lead to exhibition of several cancer hallmarks in affected cells such as sustained proliferative signaling, evasion of growth suppression, activated invasion, deregulation of cellular energetics, and avoidance of immune destruction. Similar biological changes have been observed to be a result of pathogenic viruses and, in some cases, have been linked to virus-induced cancers. Human endogenous retroviruses (HERVs), once external pathogens, now occupy more than 8% of the human genome, representing the merge of genomic and external factors. In this review, we outline all reported effects of HERVs on cancer development and discuss the HERV targets most suitable for cancer treatments as well as ongoing clinical trials for HERV-targeting drugs. We reviewed all currently available reports of the effects of HERVs on human cancers including solid tumors, lymphomas, and leukemias. Our review highlights the central roles of HERV genes, such as , , , , and in immune regulation, checkpoint blockade, cell differentiation, cell fusion, proliferation, metastasis, and cell transformation. In addition, we summarize the involvement of HERV long terminal repeat (LTR) regions in transcriptional regulation, creation of fusion proteins, expression of long non-coding RNAs (lncRNAs), and promotion of genome instability through recombination.
基因组不稳定和基因突变可导致受影响细胞呈现多种癌症特征，如持续的增殖信号传导、逃避生长抑制、激活侵袭、细胞能量代谢失调以及逃避免疫破坏。已观察到类似的生物学变化是由致病性病毒引起的，在某些情况下，还与病毒诱导的癌症有关。人类内源性逆转录病毒（HERV）曾经是外部病原体，现在占据人类基因组的8%以上，代表了基因组因素与外部因素的融合。在本综述中，我们概述了HERV对癌症发展的所有已报道影响，并讨论了最适合癌症治疗的HERV靶点以及针对HERV的药物正在进行的临床试验。我们回顾了目前所有关于HERV对人类癌症（包括实体瘤、淋巴瘤和白血病）影响的可用报告。我们的综述强调了HERV基因（如 、 、 、 和 ）在免疫调节、检查点阻断、细胞分化、细胞融合、增殖、转移和细胞转化中的核心作用。此外，我们总结了HERV长末端重复序列（LTR）区域在转录调控、融合蛋白的产生、长链非编码RNA（lncRNA）的表达以及通过重组促进基因组不稳定方面的作用。
