Hongseok Ha

Although most human endogenous retroviruses (HERVs) have been silenced and lost their ability to translocate because of accumulated mutations during evolution, they still play important roles in human biology. Several studies have demonstrated that HERVs play pathological roles in numerous human diseases, especially cancer. A few studies have revealed that long non-coding RNAs that are transcribed from HERV sequences affect cancer progression. However, there is no study on microRNAs derived from HERVs related to cancer. In this study, we identified 29 microRNAs (miRNAs) derived from HERV sequences in the human genome. In particular, we discovered that miR-4454, which is HERV-H-derived miRNA, was upregulated in non-muscle-invasive bladder cancer (NMIBC) cells. To figure out the effects of upregulated miR-4454 in NMIBC, genes whose expression was downregulated in NMIBC, as well as tumor suppressor genes, were selected as putative target genes of miR-4454. The dual-luciferase assay was used to determine the negative relationship between miR-4454 and its target genes, DNAJB4 and SASH1, and they were confirmed to be promising target genes of miR-4454. Taken together, this study suggests that the upregulation of miR-4454 derived from HERV-H in NMIBC reduces the expression of the tumor suppressor genes, DNAJB4 and SASH1, to promote NMIBC progression.

It is estimated that up to 80% of the human genome is transcribed into RNA molecules but less than 2% of the genome encodes the proteins, and the rest of the RNA transcripts that are not translated into protein are called non-coding RNAs (ncRNAs). Many studies have revealed that ncRNAs have biochemical activities as epigenetic regulators at the post-transcriptional level. Growing evidence has demonstrated that transposable elements (TEs) contribute to a large percentage of ncRNAs’ transcription. The TEs inserted into certain parts of the genome can act as alternative promoters, enhancers, and insulators, and the accumulation of TEs increases genetic diversity in the human genome. The TEs can also generate microRNAs, so-called miRNA-derived from transposable elements (MDTEs), and are also implicated in disease progression, such as infectious diseases and cancer. Here, we analyzed the origin of ncRNAs and reviewed the published literature on MDTEs related to disease progression.