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| Item Type: | Article |
|---|---|
| Title: | Human endogenous retrovirus K rec forms a regulatory loop with MITF that opposes the progression of melanoma to an invasive stage |
| Creators Name: | Singh, M., Cai, H., Bunse, M., Feschotte, C. and Izsvák, Z. |
| Abstract: | The HML2 subfamily of HERV-K (henceforth HERV-K) represents the most recently endogenized retrovirus in the human genome. While the products of certain HERV-K genomic copies are expressed in normal tissues, they are upregulated in several pathological conditions, including various tumors. It remains unclear whether HERV-K(HML2)-encoded products overexpressed in cancer contribute to disease progression or are merely by-products of tumorigenesis. Here, we focus on the regulatory activities of the Long Terminal Repeats (LTR5_Hs) of HERV-K and the potential role of the HERV-K-encoded Rec in melanoma. Our regulatory genomics analysis of LTR5_Hs loci indicates that Melanocyte Inducing Transcription Factor (MITF) (also known as binds to a canonical E-box motif (CA(C/T)GTG) within these elements in proliferative type of melanoma, and that depletion of MITF results in reduced HERV-K expression. In turn, experimentally depleting Rec in a proliferative melanoma cell line leads to lower mRNA levels of MITF and its predicted target genes. Furthermore, Rec knockdown leads to an upregulation of epithelial-to-mesenchymal associated genes and an enhanced invasion phenotype of proliferative melanoma cells. Together these results suggest the existence of a regulatory loop between MITF and Rec that may modulate the transition from proliferative to invasive stages of melanoma. Because HERV-K(HML2) elements are restricted to hominoid primates, these findings might explain certain species-specific features of melanoma progression and point to some limitations of animal models in melanoma studies. |
| Keywords: | HERV-K, Rec, LTR5_Hs, MITF, Melanoma, Proliferative, Invasive |
| Source: | Viruses |
| ISSN: | 1999-4915 |
| Publisher: | MDPI |
| Volume: | 12 |
| Number: | 11 |
| Page Range: | 1303 |
| Date: | 13 November 2020 |
| Official Publication: | https://doi.org/10.3390/v12111303 |
| PubMed: | View item in PubMed |
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