BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB

Benign melanocytic nevi frequently emerge when an acquired BRAFV600E mutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence in melanocytic nevus formation, necessitating investigations into alternati...

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Autores principales:	Andrew S McNeal, Rachel L Belote, Hanlin Zeng, Marcus Urquijo, Kendra Barker, Rodrigo Torres, Meghan Curtin, A Hunter Shain, Robert HI Andtbacka, Sheri Holmen, David H Lum, Timothy H McCalmont, Matt W VanBrocklin, Douglas Grossman, Maria L Wei, Ursula E Lang, Robert L Judson-Torres
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	melanoma melanocytes nevi microRNA Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/53ad9d885af34b1391f8b61352342926
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spelling	oai:doaj.org-article:53ad9d885af34b1391f8b613523429262021-11-23T12:30:52ZBRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB10.7554/eLife.703852050-084Xe70385https://doaj.org/article/53ad9d885af34b1391f8b613523429262021-11-01T00:00:00Zhttps://elifesciences.org/articles/70385https://doaj.org/toc/2050-084XBenign melanocytic nevi frequently emerge when an acquired BRAFV600E mutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence in melanocytic nevus formation, necessitating investigations into alternative mechanisms for the establishment and maintenance of proliferation arrest in nevi. We compared the transcriptomes of melanocytes from healthy human skin, nevi, and melanomas arising from nevi and identified a set of microRNAs as highly expressed nevus-enriched transcripts. Two of these microRNAs—MIR211-5p and MIR328-3p—induced mitotic failure, genome duplication, and proliferation arrest in human melanocytes through convergent targeting of AURKB. We demonstrate that BRAFV600E induces a similar proliferation arrest in primary human melanocytes that is both reversible and conditional. Specifically, BRAFV600E expression stimulates either arrest or proliferation depending on the differentiation state of the melanocyte. We report genome duplication in human melanocytic nevi, reciprocal expression of AURKB and microRNAs in nevi and melanomas, and rescue of arrested human nevus cells with AURKB expression. Taken together, our data describe an alternative molecular mechanism for melanocytic nevus formation that is congruent with both experimental and clinical observations.Andrew S McNealRachel L BeloteHanlin ZengMarcus UrquijoKendra BarkerRodrigo TorresMeghan CurtinA Hunter ShainRobert HI AndtbackaSheri HolmenDavid H LumTimothy H McCalmontMatt W VanBrocklinDouglas GrossmanMaria L WeiUrsula E LangRobert L Judson-TorreseLife Sciences Publications LtdarticlemelanomamelanocytesnevimicroRNAMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	melanoma melanocytes nevi microRNA Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	melanoma melanocytes nevi microRNA Medicine R Science Q Biology (General) QH301-705.5 Andrew S McNeal Rachel L Belote Hanlin Zeng Marcus Urquijo Kendra Barker Rodrigo Torres Meghan Curtin A Hunter Shain Robert HI Andtbacka Sheri Holmen David H Lum Timothy H McCalmont Matt W VanBrocklin Douglas Grossman Maria L Wei Ursula E Lang Robert L Judson-Torres BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB
description	Benign melanocytic nevi frequently emerge when an acquired BRAFV600E mutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence in melanocytic nevus formation, necessitating investigations into alternative mechanisms for the establishment and maintenance of proliferation arrest in nevi. We compared the transcriptomes of melanocytes from healthy human skin, nevi, and melanomas arising from nevi and identified a set of microRNAs as highly expressed nevus-enriched transcripts. Two of these microRNAs—MIR211-5p and MIR328-3p—induced mitotic failure, genome duplication, and proliferation arrest in human melanocytes through convergent targeting of AURKB. We demonstrate that BRAFV600E induces a similar proliferation arrest in primary human melanocytes that is both reversible and conditional. Specifically, BRAFV600E expression stimulates either arrest or proliferation depending on the differentiation state of the melanocyte. We report genome duplication in human melanocytic nevi, reciprocal expression of AURKB and microRNAs in nevi and melanomas, and rescue of arrested human nevus cells with AURKB expression. Taken together, our data describe an alternative molecular mechanism for melanocytic nevus formation that is congruent with both experimental and clinical observations.
format	article
author	Andrew S McNeal Rachel L Belote Hanlin Zeng Marcus Urquijo Kendra Barker Rodrigo Torres Meghan Curtin A Hunter Shain Robert HI Andtbacka Sheri Holmen David H Lum Timothy H McCalmont Matt W VanBrocklin Douglas Grossman Maria L Wei Ursula E Lang Robert L Judson-Torres
author_facet	Andrew S McNeal Rachel L Belote Hanlin Zeng Marcus Urquijo Kendra Barker Rodrigo Torres Meghan Curtin A Hunter Shain Robert HI Andtbacka Sheri Holmen David H Lum Timothy H McCalmont Matt W VanBrocklin Douglas Grossman Maria L Wei Ursula E Lang Robert L Judson-Torres
author_sort	Andrew S McNeal
title	BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB
title_short	BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB
title_full	BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB
title_fullStr	BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB
title_full_unstemmed	BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB
title_sort	brafv600e induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of aurkb
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/53ad9d885af34b1391f8b61352342926
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BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB

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