Diagnostic and therapeutic impact of miR-142, miR-146a, and miR-155 on cutaneous T-cell lymphoma

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). The diagnosis of early-stage MF can be very challenging due to shared clinical and histopathological features with benign inflammatory dermatoses. Moreover, a lack of understanding of the aetiopathology is having a negative impact on efficient diagnosis and therapy. State-of-the-art bioinformatics tools were used to identify differentially expressed miRNAs that are potentially involved in the molecular pathogenesis of MF, with further investigation of their potential role as diagnostic biomarkers or therapeutic targets. The expression of miRNAs (miR-26a, miR-92a, miR-106b, miR-142, miR-146a, miR-155, miR-181a, miR-222, and miR-494) was evaluated in the serum of early-stage MF patients using RT-PCR as well as skin biopsies and CTCL cell lines (MyLa and SeAx). Our data showed that these miRNAs were significantly upregulated in plasma and biopsies of early-stage MF patients and CTCL cell lines compared to controls (p<0.05). Downregulation of miR-142, miR-146a, and miR-155 in CTCL cell lines using specific antagomirs significantly decreased cell proliferation and increased apoptosis of malignant cells. Overall, detailed bioinformatics analysis, followed by experimental validation in CTCL plasma, tissues, and cell lines, indicated that detection of miR-142, miR-146a, and miR-155 upregulation by liquid biopsy may represent a potential non-invasive diagnostic technique as well as a new therapeutic targeting approach for early-stage MF.