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Background: Several cancers, including mycosis fungoides (MF), have reported dysregulation of miR‐195‐5p. miR‐195‐5p plays a role in cell cycle regulation in several malignant diseases. Objectives: This study aimed to investigate: (a) the expression level of miR‐195‐5p in lesional MF skin biopsies and (b) the potential regulatory roles of miR‐195‐5p in MF. Methods: Quantitative real‐time polymerase chain reaction (RT‐qPCR) was used to determine miR‐195‐5p expression in MF skin biopsies and cell lines. The effect of miR‐195‐5p and ADP‐ribosylation factor‐like protein 2 (ARL2) on cell cycle and apoptosis was measured by flow cytometry assays. Changes in ARL2 expression were determined by RT‐qPCR and Western blotting (WB). Results: We found lower expression levels of miR‐195‐5p in lesional skin from MF patients compared with non‐lesional MF skin and skin from healthy volunteers. Additionally, miR‐195‐5p showed lower expression levels in the skin from patients with disease progression compared with patients with stable disease. In vitro studies showed that overexpression of miR‐195‐5p induced a cell cycle arrest in G0G1. Using microarray analysis, we identified several genes that were regulated after miR‐195‐5p overexpression. The most downregulated gene after miR‐195‐5p mimic transfection was ARL2. RT‐qPCR and WB analyses confirmed downregulation of ARL2 following transfection with miR‐195‐5p mimic. Lastly, transfection with siRNA against ARL2 also induced a G0G1 arrest. Conclusion: Upregulation of miR‐195‐5p in MF inhibits cycle arrest by downregulation of ARL2. miR‐195‐5p may thus function as a tumor suppressor in MF and low miR‐195‐5p expression in lesional MF skin may promote disease progression. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to investigate the validity of a diagnostic microRNA classifier in cutaneous T-cell lymphomas (CTCL). Researchers evaluated the classifier with 78 patients using a standard TaqMan real-time quantitative polymerase chain reaction (qRT-PCR) assay. They found that while the classifier is diagnostically informative in a wide variety of malignancies, it alone is not sufficient to identify cases of CTCL.

IL-17 is a proinflammatory cytokine that is crucial for the host's protection against a range of extracellular pathogens. However, inappropriately regulated expression of IL-17 is associated with the development of inflammatory diseases and cancer. In cutaneous T-cell lymphoma (CTCL), malignant T cells gradually accumulate in skin lesions characterized by massive chronic inflammation, suggesting that IL-17 could be involved in the pathogenesis. In this study we show that IL-17 protein is present in 10 of 13 examined skin lesions but not in sera from 28 CTCL patients. Importantly, IL-17 expression is primarily observed in atypical lymphocytes with characteristic neoplastic cell morphology. In accordance, malignant T-cell lines from CTCL patients produce IL-17 and the synthesis is selectively increased by IL-2 receptor β chain cytokines. Small-molecule inhibitors or small interfering RNA against Jak3 and signal transducer and activator of transcription 3 (Stat3) reduce the production of IL-17, showing that the Jak3/Stat3 pathway promotes the expression of the cytokine. In summary, our findings indicate that the malignant T cells in CTCL lesions express IL-17 and that this expression is promoted by the Jak3/Stat3 pathway. [ABSTRACT FROM AUTHOR]