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转座子触发的先天免疫反应赋予盲鼹鼠抗癌能力
作者:小柯机器人 发布时间:2021/9/26 14:30:54

美国罗彻斯特大学Vera Gorbunova、Andrei Seluanov等研究人员合作发现,转座子触发的先天免疫反应赋予盲鼹鼠抗癌能力。相关论文于2021年9月23日在线发表于国际学术期刊《自然—免疫学》。

研究人员发现,盲鼹鼠(BMR)的抗癌性是由可逆转录元素(RTE)介导的。BMR的细胞和组织表达的DNA甲基转移酶1水平非常低。细胞增生后,BMR基因组DNA失去甲基化,导致RTE的激活。上调的RTE形成细胞质RNA-DNA杂交体,进而激活cGAS-STING途径来诱导细胞死亡。尽管这一机制在BMR中得到了加强,但研究人员表明它在小鼠和人类中都有作用。

研究人员提出,RTE被共同用作肿瘤抑制剂,监测细胞增殖,并在恶性肿瘤前的细胞中被激活,通过激活先天免疫反应引发细胞死亡。RTE的激活是一把双刃剑,既可作为肿瘤抑制剂,又可通过诱导无菌性炎症促成晚年的衰老。

据介绍,BMR是小型啮齿动物,其特点是寿命特别长(>21年),对自发和诱导的肿瘤发生都有抵抗力。

附:英文原文

Title: Transposon-triggered innate immune response confers cancer resistance to the blind mole rat

Author: Zhao, Yang, Oreskovic, Ena, Zhang, Quanwei, Lu, Quan, Gilman, Abbey, Lin, Yifei S., He, Junyue, Zheng, Zhizhong, Lu, J. Yuyang, Lee, Jina, Ke, Zhonghe, Ablaeva, Julia, Sweet, Matthew J., Horvath, Steve, Zhang, Zhengdong, Nevo, Eviatar, Seluanov, Andrei, Gorbunova, Vera

Issue&Volume: 2021-09-23

Abstract: Blind mole rats (BMRs) are small rodents, characterized by an exceptionally long lifespan (>21years) and resistance to both spontaneous and induced tumorigenesis. Here we report that cancer resistance in the BMR is mediated by retrotransposable elements (RTEs). Cells and tissues of BMRs express very low levels of DNA methyltransferase 1. Following cell hyperplasia, the BMR genome DNA loses methylation, resulting in the activation of RTEs. Upregulated RTEs form cytoplasmic RNA–DNA hybrids, which activate the cGAS–STING pathway to induce cell death. Although this mechanism is enhanced in the BMR, we show that it functions in mice and humans. We propose that RTEs were co-opted to serve as tumor suppressors that monitor cell proliferation and are activated in premalignant cells to trigger cell death via activation of the innate immune response. Activation of RTEs is a double-edged sword, serving as a tumor suppressor but contributing to aging in late life via the induction of sterile inflammation.

DOI: 10.1038/s41590-021-01027-8

Source: https://www.nature.com/articles/s41590-021-01027-8

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex