Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes

Metastatic melanoma is a deadly malignancy with poor outcomes historically. Immuno-oncology (IO) agents, targeting immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1), have revolutionized melanoma treatment and outcomes, achievi...

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Autores principales:	Robert A. Szczepaniak Sloane, Michael G. White, Russell G. Witt, Anik Banerjee, Michael A. Davies, Guangchun Han, Elizabeth Burton, Nadim Ajami, Julie M. Simon, Chantale Bernatchez, Lauren E. Haydu, Hussein A. Tawbi, Jeffrey E. Gershenwald, Emily Keung, Merrick Ross, Jennifer McQuade, Rodabe N. Amaria, Khalida Wani, Alexander J. Lazar, Scott E. Woodman, Linghua Wang, Miles C. Andrews, Jennifer A. Wargo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	microRNA melanoma immune checkpoint blockade Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c8064d6d4da44883816ebcc8ea0a1965
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spelling	oai:doaj.org-article:c8064d6d4da44883816ebcc8ea0a19652021-11-11T15:27:43ZIdentification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes10.3390/cancers132153012072-6694https://doaj.org/article/c8064d6d4da44883816ebcc8ea0a19652021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5301https://doaj.org/toc/2072-6694Metastatic melanoma is a deadly malignancy with poor outcomes historically. Immuno-oncology (IO) agents, targeting immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1), have revolutionized melanoma treatment and outcomes, achieving significant response rates and remarkable long-term survival. Despite these vast improvements, roughly half of melanoma patients do not achieve long-term clinical benefit from IO therapies and there is an urgent need to understand and mitigate mechanisms of resistance. MicroRNAs are key post-transcriptional regulators of gene expression that regulate many aspects of cancer biology, including immune evasion. We used network analysis to define two core microRNA–mRNA networks in melanoma tissues and cell lines corresponding to ‘MITF-low’ and ‘Keratin’ transcriptomic subsets of melanoma. We then evaluated expression of these core microRNAs in pre-PD-1-inhibitor-treated melanoma patients and observed that higher expression of miR-100-5p and miR-125b-5p were associated with significantly improved overall survival. These findings suggest that miR-100-5p and 125b-5p are potential markers of response to PD-1 inhibitors, and further evaluation of these microRNA–mRNA interactions may yield further insight into melanoma resistance to PD-1 inhibitors.Robert A. Szczepaniak SloaneMichael G. WhiteRussell G. WittAnik BanerjeeMichael A. DaviesGuangchun HanElizabeth BurtonNadim AjamiJulie M. SimonChantale BernatchezLauren E. HayduHussein A. TawbiJeffrey E. GershenwaldEmily KeungMerrick RossJennifer McQuadeRodabe N. AmariaKhalida WaniAlexander J. LazarScott E. WoodmanLinghua WangMiles C. AndrewsJennifer A. WargoMDPI AGarticlemicroRNAmelanomaimmune checkpoint blockadeNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5301, p 5301 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microRNA melanoma immune checkpoint blockade Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	microRNA melanoma immune checkpoint blockade Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Robert A. Szczepaniak Sloane Michael G. White Russell G. Witt Anik Banerjee Michael A. Davies Guangchun Han Elizabeth Burton Nadim Ajami Julie M. Simon Chantale Bernatchez Lauren E. Haydu Hussein A. Tawbi Jeffrey E. Gershenwald Emily Keung Merrick Ross Jennifer McQuade Rodabe N. Amaria Khalida Wani Alexander J. Lazar Scott E. Woodman Linghua Wang Miles C. Andrews Jennifer A. Wargo Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes
description	Metastatic melanoma is a deadly malignancy with poor outcomes historically. Immuno-oncology (IO) agents, targeting immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1), have revolutionized melanoma treatment and outcomes, achieving significant response rates and remarkable long-term survival. Despite these vast improvements, roughly half of melanoma patients do not achieve long-term clinical benefit from IO therapies and there is an urgent need to understand and mitigate mechanisms of resistance. MicroRNAs are key post-transcriptional regulators of gene expression that regulate many aspects of cancer biology, including immune evasion. We used network analysis to define two core microRNA–mRNA networks in melanoma tissues and cell lines corresponding to ‘MITF-low’ and ‘Keratin’ transcriptomic subsets of melanoma. We then evaluated expression of these core microRNAs in pre-PD-1-inhibitor-treated melanoma patients and observed that higher expression of miR-100-5p and miR-125b-5p were associated with significantly improved overall survival. These findings suggest that miR-100-5p and 125b-5p are potential markers of response to PD-1 inhibitors, and further evaluation of these microRNA–mRNA interactions may yield further insight into melanoma resistance to PD-1 inhibitors.
format	article
author	Robert A. Szczepaniak Sloane Michael G. White Russell G. Witt Anik Banerjee Michael A. Davies Guangchun Han Elizabeth Burton Nadim Ajami Julie M. Simon Chantale Bernatchez Lauren E. Haydu Hussein A. Tawbi Jeffrey E. Gershenwald Emily Keung Merrick Ross Jennifer McQuade Rodabe N. Amaria Khalida Wani Alexander J. Lazar Scott E. Woodman Linghua Wang Miles C. Andrews Jennifer A. Wargo
author_facet	Robert A. Szczepaniak Sloane Michael G. White Russell G. Witt Anik Banerjee Michael A. Davies Guangchun Han Elizabeth Burton Nadim Ajami Julie M. Simon Chantale Bernatchez Lauren E. Haydu Hussein A. Tawbi Jeffrey E. Gershenwald Emily Keung Merrick Ross Jennifer McQuade Rodabe N. Amaria Khalida Wani Alexander J. Lazar Scott E. Woodman Linghua Wang Miles C. Andrews Jennifer A. Wargo
author_sort	Robert A. Szczepaniak Sloane
title	Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes
title_short	Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes
title_full	Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes
title_fullStr	Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes
title_full_unstemmed	Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes
title_sort	identification of microrna–mrna networks in melanoma and their association with pd-1 checkpoint blockade outcomes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c8064d6d4da44883816ebcc8ea0a1965
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Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes

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