Human Endogenous Retrovirus K in Cancer: A Potential Biomarker and Immunotherapeutic Target

Abstract

<jats:p>In diseases where epigenetic mechanisms are changed, such as cancer, many genes show altered gene expression and inhibited genes become activated. Human endogenous retrovirus type K (HERV-K) expression is usually inhibited in normal cells from healthy adults. In tumor cells, however, HERV-K mRNA expression has been frequently documented to increase. Importantly, HERV-K-derived proteins can act as tumor-specific antigens, a class of neoantigens, and induce immune responses in different types of cancer. In this review, we describe the function of the HERV-K HML-2 subtype in carcinogenesis as biomarkers, and their potential as targets for cancer immunotherapy.</jats:p>

Human Endogenous Retroviruses Long Terminal Repeat Methylation, Transcription, and Protein Expression in Human Colon Cancer

“…These HERVs were chosen due to their possible relationship with cancer: HERV-H, among the known HERVs, is the principal candidate for the colon cancer pathogenesis (17), while the function of the HERV-K HML-2 subtype in carcinogenesis as biomarkers and their potential as targets for cancer are welldescribed (16). HERV P has been also found differentially expressed in colon cancer tissues (18).…”

“…The HERV-H env was selected because it is entirely present on the chr2q24.3. However, it has been reported that HERV-H env fragments can be found on human chromosomes 1, 2, 3, 4, 5,6,7,9,10,11,12,14,15,16,17,18,19,20, X, and Y, and they all might be subjected to change in the expression. To avoid this limitation, the future project will be focused on more HERV-H insertions, designing a specific PCR for each insertion, so that it could be possible identifying which one might be involved in the colon cancer pathogenesis.…”

“…It has also been suggested that some HERV-related proteins may act as cancerspecific antigens and therefore may constitute a novel target for immunotherapy (15). Among all the HERVs, one of the mostly studied for its involvement in the human tumorigenesis is the HERV-K (HML-2) (16). Nonetheless, data with regard to colon cancer are scarce and currently limited to a few reports showing overexpression of HERV-H genes in tumor tissues compared to normal tissues retrieved from negative surgical margins (17).…”

Human Endogenous Retrovirus Expression Is Upregulated in the Breast Cancer Microenvironment of HIV Infected Women: A Pilot Study

“…Moreover, HERV-L shows elevated numbers of somatic single-nucleotide variations in cancer (68), which may impact cancer progression. In addition, HERVs are able to induce carcinogenesis and cancer progression by regulating nearby host genes (12,69,70). Herein we reported positive association between expression of some HERVs and their neighbor genes.…”

Recognize Yourself—Innate Sensing of Non-LTR Retrotransposons

“…In addition, an aberrant expression of HERV transcripts has been observed in various inflammatory diseases and tumor samples. For example, a role of HERV transcripts in autoinflammatory diseases such as multiple sclerosis (HERV-W) or in cancer development (HERV-K) has been suggested (reviewed in [ 13 , 14 ]). In general, HERVs have been highly mutated over the course of millions of years of vertical transmission, and most of the time only solitary LTRs can be detected within the human genome.…”