Papadavid E, Braoudaki M, Bourdakou M, Lykoudi A, Nikolaou V, Tounta G, Ekonomidi A, Athanasiadis E, Spyrou G, Antoniou C, Kitsiou-Tzeli S, Rigopoulos D, Kolialexi A
1st Department of Dermatology and Cutaneous Lymphoma Clinic, Andreas Sygros Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.
2nd Departments of Dermatology and Cutaneous Lymphoma clinic, Attikon Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Tumour Biol. 2016 Nov;37(11):14667-14675. doi: 10.1007/s13277-016-5325-2. Epub 2016 Sep 13.
Herein, miRNA candidates relevant to mycosis fungoides were investigated to provide data on the molecular mechanisms underlying the pathogenesis of the disease. The miRNA expression profile of skin biopsies from patients with tumor stage MF (tMF) and normal donors was compared using miRNA microarrays. Overall, 154 miRNAs were found differentially expressed between tMF and the control cohort with the majority of them being up-regulated (57 %). Among the upregulated miRNAs, miR-3177, miR-514b-3p, miR-1267, and miR-1282 were exclusively detected in 70 % of tMF. Additional upregulated miRNAs included miR-34a, miR-29a, let-7a*, and miR-210, while miR-200c* was identified among the downregulated ones. Quantitative real-time polymerase chain reaction was used to further investigate the expression profiles of miR-34a and miR-29a and validated the overexpression of miR-34a. Enrichment studies revealed that the target genes of the differentially expressed miRNAs were important in several cancer-related signaling pathways. The overlapping relationship of the target genes among tMF, Sezary syndrome, and atopic dermatitis revealed several common and disease-specific genes. Collectively, our study modulated miR-34a as a candidate oncogenic molecule and miR-29a as a putative tumor suppressor highlighting their promising potential in the molecular pathogenesis of tMF.
在此,对与蕈样肉芽肿相关的微小RNA(miRNA)候选物进行了研究,以提供有关该疾病发病机制的分子机制数据。使用miRNA微阵列比较了肿瘤期蕈样肉芽肿(tMF)患者和正常供体皮肤活检组织的miRNA表达谱。总体而言,发现154种miRNA在tMF和对照队列之间差异表达,其中大多数上调(57%)。在上调的miRNA中,miR-3177、miR-514b-3p、miR-1267和miR-1282仅在70%的tMF中检测到。其他上调的miRNA包括miR-34a、miR-29a、let-7a和miR-210,而miR-200c在下调的miRNA中被鉴定出来。使用定量实时聚合酶链反应进一步研究miR-34a和miR-29a的表达谱,并验证了miR-34a的过表达。富集研究表明,差异表达的miRNA的靶基因在几种癌症相关信号通路中很重要。tMF、Sezary综合征和特应性皮炎靶基因的重叠关系揭示了一些共同和疾病特异性基因。总体而言,我们的研究将miR-34a调节为候选致癌分子,将miR-29a调节为假定的肿瘤抑制因子,突出了它们在tMF分子发病机制中的潜在前景。