Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides

Large cell transformation of mycosis fungoides (LCT-MF) occurs in 20–50% of advanced MF and is generally associated with poor response and dismal prognosis. Although different mechanisms have been proposed to explain the pathogenesis, little is known about the role of microRNAs (miRs) in transcripti...

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Autores principales:	Cosimo Di Raimondo, Zhen Han, Chingyu Su, Xiwei Wu, Hanjun Qin, James F. Sanchez, Yate-Ching Yuan, Xochiquetzal Martinez, Farah Abdulla, Jasmine Zain, Chun-Wei Chen, Steven T. Rosen, Christiane Querfeld
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cutaneous T-cell lymphoma (CTCL) mycosis fungoides (MF) large cell transformation of mycosis fungoides (LCT-MF) miR regulatory network tumor immune microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/10bbdfc675d14fd0b00bb999377c7d5d
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spelling	oai:doaj.org-article:10bbdfc675d14fd0b00bb999377c7d5d2021-11-25T17:04:46ZIdentification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides10.3390/cancers132258542072-6694https://doaj.org/article/10bbdfc675d14fd0b00bb999377c7d5d2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5854https://doaj.org/toc/2072-6694Large cell transformation of mycosis fungoides (LCT-MF) occurs in 20–50% of advanced MF and is generally associated with poor response and dismal prognosis. Although different mechanisms have been proposed to explain the pathogenesis, little is known about the role of microRNAs (miRs) in transcriptional regulation of LCT-MF. Here, we investigated the miR and mRNA expression profile in lesional skin samples of patients with LCT-MF and non-LCT MF using RNA-seq analysis. We found miR-146a and miR-21 to be significantly upregulated, and miR-708 the most significantly downregulated miR in LCT-MF. Integration of miR and mRNA expression profiles revealed the miR-regulated networks in LCT-MF. Ingenuity pathway analysis (IPA) demonstrated the involvement of genes for ICOS-ICOSL, PD1-PDL1, NF-κB, E2F transcription, and molecular mechanisms of cancer signaling pathways. Quantitative real time (qRT)-PCR results of target genes were consistent with the RNA-seq data. We further identified the immunosuppressive tumor microenvironment (TME) in LCT-MF. Moreover, our data indicated that miR-146a, -21 and -708 are associated with the immunosuppressive TME in LCT-MF. Collectively, our results suggest that the key LCT-MF associated miRs and their regulated networks may provide insights into its pathogenesis and identify promising targets for novel therapeutic strategies.Cosimo Di RaimondoZhen HanChingyu SuXiwei WuHanjun QinJames F. SanchezYate-Ching YuanXochiquetzal MartinezFarah AbdullaJasmine ZainChun-Wei ChenSteven T. RosenChristiane QuerfeldMDPI AGarticlecutaneous T-cell lymphoma (CTCL)mycosis fungoides (MF)large cell transformation of mycosis fungoides (LCT-MF)miR regulatory networktumor immune microenvironmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5854, p 5854 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cutaneous T-cell lymphoma (CTCL) mycosis fungoides (MF) large cell transformation of mycosis fungoides (LCT-MF) miR regulatory network tumor immune microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cutaneous T-cell lymphoma (CTCL) mycosis fungoides (MF) large cell transformation of mycosis fungoides (LCT-MF) miR regulatory network tumor immune microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cosimo Di Raimondo Zhen Han Chingyu Su Xiwei Wu Hanjun Qin James F. Sanchez Yate-Ching Yuan Xochiquetzal Martinez Farah Abdulla Jasmine Zain Chun-Wei Chen Steven T. Rosen Christiane Querfeld Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides
description	Large cell transformation of mycosis fungoides (LCT-MF) occurs in 20–50% of advanced MF and is generally associated with poor response and dismal prognosis. Although different mechanisms have been proposed to explain the pathogenesis, little is known about the role of microRNAs (miRs) in transcriptional regulation of LCT-MF. Here, we investigated the miR and mRNA expression profile in lesional skin samples of patients with LCT-MF and non-LCT MF using RNA-seq analysis. We found miR-146a and miR-21 to be significantly upregulated, and miR-708 the most significantly downregulated miR in LCT-MF. Integration of miR and mRNA expression profiles revealed the miR-regulated networks in LCT-MF. Ingenuity pathway analysis (IPA) demonstrated the involvement of genes for ICOS-ICOSL, PD1-PDL1, NF-κB, E2F transcription, and molecular mechanisms of cancer signaling pathways. Quantitative real time (qRT)-PCR results of target genes were consistent with the RNA-seq data. We further identified the immunosuppressive tumor microenvironment (TME) in LCT-MF. Moreover, our data indicated that miR-146a, -21 and -708 are associated with the immunosuppressive TME in LCT-MF. Collectively, our results suggest that the key LCT-MF associated miRs and their regulated networks may provide insights into its pathogenesis and identify promising targets for novel therapeutic strategies.
format	article
author	Cosimo Di Raimondo Zhen Han Chingyu Su Xiwei Wu Hanjun Qin James F. Sanchez Yate-Ching Yuan Xochiquetzal Martinez Farah Abdulla Jasmine Zain Chun-Wei Chen Steven T. Rosen Christiane Querfeld
author_facet	Cosimo Di Raimondo Zhen Han Chingyu Su Xiwei Wu Hanjun Qin James F. Sanchez Yate-Ching Yuan Xochiquetzal Martinez Farah Abdulla Jasmine Zain Chun-Wei Chen Steven T. Rosen Christiane Querfeld
author_sort	Cosimo Di Raimondo
title	Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides
title_short	Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides
title_full	Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides
title_fullStr	Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides
title_full_unstemmed	Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides
title_sort	identification of a distinct mirna regulatory network in the tumor microenvironment of transformed mycosis fungoides
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/10bbdfc675d14fd0b00bb999377c7d5d
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Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides

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