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Human endogenous retrovirus K rec forms a regulatory loop with MITF that opposes the progression of melanoma to an invasive stage

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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. and Cai, H. and Bunse, M. and 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
Page Range:1303
Date:13 November 2020
Official Publication:https://doi.org/10.3390/v12111303
PubMed:View item in PubMed
Related to:
https://edoc.mdc-berlin.de/18993/Preprint version

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