Human endogenous retroviruses (HERV) are remnants of exogenous retroviral infections, representing 8% of the human genome. Their regulation is based on the DNA methylation of promoters, the long terminal repeats (LTRs). Transcripts from HERV have been associated with cancers, but reports concerning HERV expression in colorectal cancer remain sporadic. Sixty-three patients with advanced stages of colorectal cancer were enrolled in this study. The expressions of HERV env gene, and HERV-H, -K, -R and -P LTRs and Alu, LINE-1 methylation levels, were investigated in the tumor, normal adjacent tissues, and, where possible, blood and plasmatic extracellular vesicles (EVs). Associations among HERV env expression, methylation status and clinical characteristics were evaluated. No differences were observed in HERV env gene expression levels among the clinical specimens, while Alu, LINE-1, HERV-H and -K LTRs were demethylated in the tumor compared to the normal adjacent tissues (p < 0.05).The HERV env gene was expressed in the EVs at of 54% (-H), 38% (-K), 31% (-R) patients. Association was not found between HERV env expression and LTR methylation, but significant higher expression of HERV-P and -R env was found in tumor tissues arising from the right colon. Our findings do not demonstrate significant overexpression of the studied HERV in colorectal cancer, but their association with tumor localization and specificity of the changes in DNA methylation of retroelements are shown. HERV sequences were packaged in the EVs and might be transferred from one cell to another.

中文翻译：

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人内源性逆转录病毒在大肠癌患者中表达基因表达和长末端重复甲基化。

人内源性逆转录病毒（HERV）是外源性逆转录病毒感染的残留物，占人类基因组的8％。它们的调节基于启动子的DNA甲基化，即长末端重复序列（LTR）。HERV的转录本与癌症有关，但有关HERV在大肠癌中表达的报道仍然很少。这项研究纳入了63位晚期结直肠癌患者。在肿瘤，正常邻近组织以及可能的情况下，在血液和血浆胞外小泡中研究了HERV env基因，HERV-H，-K，-R和-P LTR和Alu，LINE-1甲基化水平的表达（EV）。HERV env之间的关联评价其表达，甲基化状态和临床特征。在HERV没有观察到差异的env基因表达水平的临床标本中，而ALU，LINE-1，HERV-H和-K的LTR被在肿瘤去甲基化相比于正常相邻组织（p  <0.05）。HERV包膜基因在EV中有54％（-H），38％（-K），31％（-R）患者表达。在HERV env表达与LTR甲基化之间未发现关联，但HERV-P和-R env的表达明显较高在右结肠所产生的肿瘤组织中发现了这种病毒。我们的发现并未证明所研究的HERV在大肠癌中有明显的过表达，但显示了它们与肿瘤定位和反义DNA DNA甲基化变化特异性的关联。HERV序列包装在电动汽车中，可能从一个细胞转移到另一个细胞。