ABSTRACT
Localized cutaneous leishmaniasis (LCL) is a chronic disease characterized by ulcerated skin lesion(s) and uncontrolled inflammation. The mechanisms underlying the pathogenesis of LCL are not completely understood, and little is known about posttranscriptional regulation during LCL. MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression and can be implicated in the pathogenesis of LCL. We investigated the involvement of miRNAs and their targets genes in human LCL using publicly available transcriptome data sets followed by ex vivo validation. Initial analysis highlighted that miRNA expression is altered during LCL, as patients clustered separately from controls. Joint analysis identified eight high confidence miRNAs that had altered expression (-1.5 ≤ fold change ≥ 1.5; p < 0.05) between cutaneous ulcers and uninfected skin. We found that the expression of miR-193b and miR-671 are greatly associated with their target genes, CD40 and TNFR, indicating the important role of these miRNAs in the expression of genes related to the inflammatory response observed in LCL. In addition, network analysis revealed that miR-193b, miR-671, and TREM1 correlate only in patients who show faster wound healing (up to 59 days) and not in patients who require longer cure times (more than 60 days). Given that these miRNAs are associated with control of inflammation and healing time, our findings reveal that they might influence the pathogenesis and prognosis of LCL.
Subject(s)
Leishmania braziliensis/physiology , Leishmaniasis, Cutaneous/genetics , MicroRNAs/genetics , Triggering Receptor Expressed on Myeloid Cells-1/genetics , Biomarkers, Pharmacological , CD40 Antigens/genetics , Gene Expression Profiling , Gene Expression Regulation , Gene Regulatory Networks , Humans , Leishmaniasis, Cutaneous/drug therapy , Receptors, Tumor Necrosis Factor, Type I/genetics , Skin Physiological Phenomena/genetics , Treatment Outcome , Wound Healing/geneticsABSTRACT
INTRODUCTION: The forkhead box P3 (FOXP3) plays a role in cell development and control. In the presence of abnormal FOXP3 expression, tumor cells may evade the immunosurveillance of lymphoid cells, the first step for the maintenance of cancer cells in the thyroid tissue. OBJECTIVE: To identify the presence of FOXP3 in papillary thyroid carcinoma (PTC) with and without Hashimoto's Thyroiditis (HT). METHODS: We conducted a series study of cases collected from 2000 to 2008, when 1,438 thyroidectomies were performed. We selected those diagnosed with PTC, comprising 466 cases. 30 patients were randomly selected for purposes of immunohistochemistry with antibodies against FOXP3. RESULT: FOXP3 revealed high positivity for PTC and positive immunostaining was present in 21 (72.4%) from all analyzed cases. There was no difference regarding coexistent HT or not. DISCUSSION AND CONCLUSION: In the present study, it was evidenced that the focal or diffuse FOXP3 expression was commonly observed in neoplastic cells from PTC, hence indicating that the assessment of this molecule expression in suspected cases of thyroid cancer may contribute to its diagnosis.
INTRODUÇÃO: O forkhead box P3 (FOXP3) tem o seu papel no desenvolvimento e no controle celular. Na presença de alterações da sua expressão, células tumorais podem escapar da imunovigilância das células linfoides, sendo o primeiro passo para perpetuação das células cancerígenas no tecido tireoidiano. OBJETIVO: Identificar a presença do FOXP3 no carcinoma papilífero da tireoide (CPT), com e sem tireoidite de Hashimoto (TH). MÉTODOS: Foi realizado um estudo de série de casos coletados no período de 2000 a 2008, quando foram realizadas 1.438 tireoidectomias. Destes, foram selecionados aqueles que apresentaram diagnóstico de CPT, perfazendo um total de 466 casos. Desse total, 30 casos de CPT foram selecionados aleatoriamente para fins de exame imuno-histoquímico com o anticorpo contra o FOXP3. RESULTADO: O FOXP3 apresentou alta positividade no CPT; a marcação positiva na imuno-histoquímica esteve presente em 21 (72,4%) de todos os casos analisados. Não houve diferença com relação à coexistência ou não de TH. DISCUSSÃO E CONCLUSÃO: No presente estudo, foi documentado que a expressão difusa ou focal de FOXP3 foi intensamente observada nas células neoplásicas do CPT, indicando que a avaliação da expressão dessa molécula em casos suspeitos de neoplasia da tireoide pode contribuir para o seu diagnóstico.
