{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:40:25Z","timestamp":1792813225156,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NCI Cancer Center Support Grant; NIH\/NCI grant","award":["P30CA033572; R01 CA229510-01"],"award-info":[{"award-number":["P30CA033572; R01 CA229510-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Large cell transformation of mycosis fungoides (LCT-MF) occurs in 20\u201350% 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-\u03baB, 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.<\/jats:p>","DOI":"10.3390\/cancers13225854","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T02:55:17Z","timestamp":1637636117000},"page":"5854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4691-9381","authenticated-orcid":false,"given":"Cosimo","family":"Di Raimondo","sequence":"first","affiliation":[{"name":"Division of Dermatology, City of Hope, Duarte, CA 91010, USA"},{"name":"Department of Dermatology, University of Roma Tor Vergata, Rome 00133, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Dermatology, City of Hope, Duarte, CA 91010, USA"},{"name":"Beckman Research Institute, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chingyu","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Dermatology, City of Hope, Duarte, CA 91010, USA"},{"name":"Beckman Research Institute, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, City of Hope, Duarte, CA 91010, USA"},{"name":"Integrative Genomics Core, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjun","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, City of Hope, Duarte, CA 91010, USA"},{"name":"Integrative Genomics Core, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Beckman Research Institute, City of Hope, Duarte, CA 91010, USA"},{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3698-9784","authenticated-orcid":false,"given":"Yate-Ching","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Computational Quantitative Medicine, City of Hope, Duarte, CA 91010, USA"},{"name":"Translational Bioinformatics, Center for Informatics, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xochiquetzal","family":"Martinez","sequence":"additional","affiliation":[{"name":"Division of Dermatology, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Abdulla","sequence":"additional","affiliation":[{"name":"Division of Dermatology, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Zain","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8737-6830","authenticated-orcid":false,"given":"Chun-Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Beckman Research Institute, City of Hope, Duarte, CA 91010, USA"},{"name":"Department of Systems Biology, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Beckman Research Institute, City of Hope, Duarte, CA 91010, USA"},{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9698-5809","authenticated-orcid":false,"given":"Christiane","family":"Querfeld","sequence":"additional","affiliation":[{"name":"Division of Dermatology, City of Hope, Duarte, CA 91010, USA"},{"name":"Beckman Research Institute, City of Hope, Duarte, CA 91010, USA"},{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA"},{"name":"Department of Pathology, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205.e1","DOI":"10.1016\/j.jaad.2013.07.049","article-title":"Primary cutaneous T-cell lymphoma (mycosis fungoides and S\u00e9zary syndrome)","volume":"70","author":"Jawed","year":"2014","journal-title":"J. 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