PMID- 30431147 OWN - NLM STAT- MEDLINE DCOM- 20200731 LR - 20211204 IS - 1365-2133 (Electronic) IS - 0007-0963 (Linking) VI - 180 IP - 5 DP - 2019 May TI - Unilesional mycosis fungoides is associated with increased expression of microRNA-17~92 and T helper 1 skewing. PG - 1123-1134 LID - 10.1111/bjd.17425 [doi] AB - BACKGROUND: The molecular basis of unilesional mycosis fungoides (MF), characterized by a solitary lesion that is clinicopathologically indistinguishable from multifocal patch or plaque MF (early MF), is unknown. OBJECTIVES: To investigate the microRNA profile in unilesional MF distinguishing it from early MF. METHODS: Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix microRNA array, with further comparison with inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyse the gene expression of T helper (Th)1 immune markers, and immunohistochemistry was used to evaluate CXCR3 and GATA-binding protein 3 (GATA3) markers for Th1 and Th2 cells, respectively. RESULTS: Unilesional MF had a significantly higher level of expression of all members of the microRNA miR-17~92 cluster than early MF. Specifically, unilesional MF had a higher miR-17 level than early MF and inflammatory dermatoses. There was downregulation of the expression of phosphatase and tensin homolog (PTEN) and CREB1, known targets of miR-17~92 members; higher gene expression of interleukin-2 and interferon-gamma; and a statistically lower average percentage of GATA3(+) dermal cells (6.7% vs. 42.3%), were detected in unilesional MF compared with early MF. High immunoreactivity of CXCR3 was noted in both unilesional and early MF. CONCLUSIONS: Unilesional MF exhibits a microRNA profile distinct from that of conventional early MF, with a higher level of miR-17~92 members along with Th1 skewing. These findings suggest a robust reactive T-cell immune response in unilesional MF and might account for the localized nature of this disease. CI - (c) 2018 British Association of Dermatologists. FAU - Moyal, L AU - Moyal L AUID- ORCID: 0000-0002-3076-1527 AD - Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel. AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. FAU - Gorovitz-Haris, B AU - Gorovitz-Haris B AD - Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel. AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. FAU - Yehezkel, S AU - Yehezkel S AD - Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel. AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. FAU - Jacob-Hirsch, J AU - Jacob-Hirsch J AD - Cancer Research Center, Sheba Medical Center, Tel Hashomer, Israel. FAU - Bershtein, V AU - Bershtein V AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. FAU - Barzilai, A AU - Barzilai A AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel. FAU - Rotem, C AU - Rotem C AD - Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel. AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. FAU - Sherman, S AU - Sherman S AD - Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel. AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. FAU - Amitay-Laish, I AU - Amitay-Laish I AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. FAU - Feinmesser, M AU - Feinmesser M AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Institute of Pathology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. FAU - Hodak, E AU - Hodak E AD - Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel. AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. LA - eng PT - Journal Article DEP - 20190124 PL - England TA - Br J Dermatol JT - The British journal of dermatology JID - 0004041 RN - 0 (CXCR3 protein, human) RN - 0 (GATA3 Transcription Factor) RN - 0 (GATA3 protein, human) RN - 0 (MIR17HG, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (Receptors, CXCR3) SB - IM CIN - Br J Dermatol. 2019 May;180(5):984-985. PMID: 31025731 MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Biopsy MH - Female MH - GATA3 Transcription Factor/metabolism MH - Gene Expression Regulation, Neoplastic/*immunology MH - Humans MH - Male MH - MicroRNAs/*metabolism MH - Middle Aged MH - Mycosis Fungoides/*genetics/immunology/pathology MH - RNA, Long Noncoding MH - Receptors, CXCR3/metabolism MH - Skin/immunology/pathology MH - Skin Neoplasms/*genetics/immunology/pathology MH - Th1 Cells/*immunology/metabolism MH - Th2 Cells/immunology/metabolism MH - Young Adult EDAT- 2018/11/16 06:00 MHDA- 2020/08/01 06:00 CRDT- 2018/11/16 06:00 PHST- 2018/11/08 00:00 [accepted] PHST- 2018/11/16 06:00 [pubmed] PHST- 2020/08/01 06:00 [medline] PHST- 2018/11/16 06:00 [entrez] AID - 10.1111/bjd.17425 [doi] PST - ppublish SO - Br J Dermatol. 2019 May;180(5):1123-1134. doi: 10.1111/bjd.17425. Epub 2019 Jan 24.