Intrinsic reactivation of human endogenous retroviruses in the osteosarcoma

Abstract

The human genome contains human endogenous retroviruses (HERVs) and they occupy around 8% of our genome. These viruses are derived from ancient infections of retroviruses that were reverse transcribed and integrated into the genome of ancestral host animals. These viral genomes were fixed and inherited for tens of millions of years ago. Almost all of the HERVs have lost their infectivity and no known HERV is presently. The role of HERVs has been shown in the different inflammatory diseases and cancers. The goal of present study was to analyse the genome-wide transcriptional activity of HERVs in osteosarcoma. We performed RNA-seq analysis of 36 tumor-normal paired samples, raw sequencing data were used to identify HERV sequences and counts data as expressional activity. DESeq2 package was used for statistical analysis. We found massive and activation of HERVs in the osteosarcoma sample. More precisely, 58 different repeat element were differently described between normal and tumor bone with the FDR levele below 0.05. The most significantly upregulated elements were satellite elements ALR, ALR/ALPHA, ALR2, ALR6 and ALRA SAT elements. In addition, over-expression of the pericentromeric human satellite II (HSATII) and the ancient mariner transposon (HSMAR1) was found. The most down-regulated elements were HERVK22I, LTR40A, LTR40B, LTR40C and MER87B. Up-regulation of the satellite elements during cancer has been described in some previous studies. However, genome-wide analysis of all repetitive elements in the human genome is novel approach and could give additional information about the oncogenesis