Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

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

[img]
Preview
PDF (Preprint) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB
Item Type:Preprint
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 Izsvak, Z.
Abstract:In the human genome, HERV-K(HML2) is the most recently endogenized retrovirus (ERV). While HERV-K(HML2) transcription is observed in healthy tissues, various cancers showed the upregulation of retroviral derived endogenized accessory products (e.g., envelope (Env), Np9 and Rec). Still, it is not clear whether the different HERV-K-derived genes contribute to a disease, or they are mere by-products. Here, we focus on the potential role of Rec in melanoma. Our in vitro model and high throughput data mining, including single-cell transcriptome analyses of patent’s material, reveal that Rec expression marks the proliferative (still controllable) stage of melanoma, and is involved in maintaining a delicate balance between cell proliferation and invasion. Thus, similar to melanocyte-inducing transcription factor (MITF), Rec is a sensitive marker of melanoma progression. Our Rec-knockdown in vitro system can faithfully model a subpopulation (MITF malignancy) of melanoma cells in human patients. Like Env, Rec modulates an endothelial-mesenchymal transition (EMT)-like process of cancer progression; however, they seem to affect the phenotype switch inversely. Rec inhibits the transition to the invasive state by altering the expression level of some key determinants of the EMT-like process, including MITF that directly binds the LTR5 _Hs of HERV-K. The Hominoid-specific HERV-K products might explain certain species-specific features of melanoma progression, and pinpoint to the limitation of using animal models in melanoma studies.
Keywords:HERV-K, Rec, Melanoma, Metastasis, MITF
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.05.27.120170
Date:2 June 2020
Official Publication:https://doi.org/10.1101/2020.05.27.120170

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library