MicroRNA profiling reveals that miR-21, miR486 and miR-214 are upregulated and involved in cell survival in Sézary syndrome

Abstract

Sézary syndrome (SS) is an incurable leukemic variant of cutaneous T-cell lymphoma and its pathogenesis is still unknown. Diagnosis/prognosis may strongly ameliorate the management of SS individuals. Here, we profiled the expression of 470 microRNAs (miRNAs) in a cohort of 22 SS patients, and we identified 45 miRNAs differentially expressed between SS and controls. Using predictive analysis, a list of 19 miRNAs, including miR-21, miR-214, miR-486, miR-18a, miR-342, miR-31 and let-7 members were also found. Moreover, we defined a signature of 14 miRNAs including again miR-21, potentially able to discriminate patients with unfavorable and favorable outcome. We validated our data for miR-21, miR-214 and miR-486 by qRT-PCR, including an additional set of array-independent SS cases. In addition, we also provide an in vitro evidence for a contribution of miR-214, miR-486 and miR-21 to apoptotic resistance of CTCL cell line.

miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops

“…It has been reported that miR-486 is overexpressed in Sézary syndrome, K-ras mutated colorectal carcinoma and bronchioalveolar stem cells [42][43][44]. Importantly, Hu et al [45] found that non-small cell lung cancer patients with high serum levels of miR-486 have shorter overall survival times.…”

MicroRNA-mediated Gene Expression in Sezary Syndrome: An Overview

“…In addition, performing functional experiments, this authors observed that all these miRs are able to promote cell survival in CTCL cell line. Moreover, miR-214 over-expression has also been recently reported to promote proliferation of healthy T lymphocytes via PTEN targeting [50] whereas miR-486 is located on chromosome 8p11.21, a frequent gain region in this pathology [4]. We recently demonstrated that miR-21, miR-106b and miR-486 modulate PTEN levels in vitro [43].…”

“…In a recent study, Litvinov et al demonstrated that STAT4 is one of the targets of miR-155 [46]. In summary, STAT signaling appears to play a central role in the pathogenesis of this cancer where early in the disease STAT5 up-regulation drives the expression of miR-155 oncogene, [4]. Their results indicated that miR-214 and miR-486 were over-expressed in the majority of SS patients therefore more likely related to diagnosis, whereas miR-21 up-regulation is detected in a smaller number of patients thereby more probably associated to prognosis of SS.…”

“…"cerebriform") nuclei in patients with Mycosis Fungoides (MF) or SS [1][2] [3]. In SS, these clonal T cells are generally CD31, CD41 and CD82 by multicolor flow cytometry and are present in skin, lymph nodes and peripheral blood [4] [5]. The aberrant loss of pan-T-cell antigens, including CD2, CD3, CD4, CD5, and CD7, is frequently observed [6] [7].…”

“…These regions are likely to contain genes involved in the development of SS. Gene expression analysis has revealed several genes that are significantly over-expressed in SS [21] (such as DNM3, cMyc, TWIST1 and TNFSF11) or down-regulated [4][22] (such as STAT4 and PTEN), that are correlated to microRNA expression ( …”