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转座元件在衰老和癌症中的作用。

The role of transposable elements in aging and cancer.

机构信息

Medicinal Plants Processing Research Center, School of Pharmacy, Shiraz University of Medical Science, Shiraz, Iran.

Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Biogerontology. 2023 Aug;24(4):479-491. doi: 10.1007/s10522-023-10028-z. Epub 2023 Apr 5.

Abstract

Transposable elements (TEs) constitute a large portion of the human genome. Various mechanisms at the transcription and post-transcription levels developed to suppress TE activity in healthy conditions. However, a growing body of evidence suggests that TE dysregulation is involved in various human diseases, including age-related diseases and cancer. In this review, we explained how sensing TEs by the immune system could induce innate immune responses, chronic inflammation, and following age-related diseases. We also noted that inflammageing and exogenous carcinogens could trigger the upregulation of TEs in precancerous cells. Increased inflammation could enhance epigenetic plasticity and upregulation of early developmental TEs, which rewires the transcriptional networks and gift the survival advantage to the precancerous cells. In addition, upregulated TEs could induce genome instability, activation of oncogenes, or inhibition of tumor suppressors and consequent cancer initiation and progression. So, we suggest that TEs could be considered therapeutic targets in aging and cancer.

摘要

转座元件 (TEs) 构成了人类基因组的很大一部分。在转录和转录后水平上发展了各种机制来抑制健康条件下的 TE 活性。然而,越来越多的证据表明,TE 失调与各种人类疾病有关,包括与年龄相关的疾病和癌症。在这篇综述中,我们解释了免疫系统如何通过感知 TE 来引发先天免疫反应、慢性炎症以及随后的与年龄相关的疾病。我们还注意到,炎症和外源性致癌剂可能会引发癌前细胞中 TE 的上调。增加的炎症可以增强表观遗传可塑性和早期发育 TE 的上调,这会重新布线转录网络,并为癌前细胞提供生存优势。此外,上调的 TE 可诱导基因组不稳定性、癌基因的激活或肿瘤抑制基因的抑制,从而导致癌症的发生和进展。因此,我们认为 TE 可以被视为衰老和癌症的治疗靶点。

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