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

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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.

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Most cited references 24

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Origins and Mechanisms of miRNAs and siRNAs.

Richard W. Carthew, Erik J. Sontheimer (2009)

Over the last decade, approximately 20-30 nucleotide RNA molecules have emerged as critical regulators in the expression and function of eukaryotic genomes. Two primary categories of these small RNAs--short interfering RNAs (siRNAs) and microRNAs (miRNAs)--act in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Recent advances have revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access. Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment.

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miR-21-mediated tumor growth.

M-L Si, S Zhu, H. Wu … (2007)

MicroRNAs (miRNAs) are approximately 22 nucleotide non-coding RNA molecules that regulate gene expression post-transcriptionally. Although aberrant expression of miRNAs in various human cancers suggests a role for miRNAs in tumorigenesis, it remains largely unclear as to whether knockdown of a specific miRNA affects tumor growth. In this study, we profiled miRNA expression in matched normal breast tissue and breast tumor tissues by TaqMan real-time polymerase chain reaction miRNA array methods. Consistent with previous findings, we found that miR-21 was highly overexpressed in breast tumors compared to the matched normal breast tissues among 157 human miRNAs analysed. To better evaluate the role of miR-21 in tumorigenesis, we transfected breast cancer MCF-7 cells with anti-miR-21 oligonucleotides and found that anti-miR-21 suppressed both cell growth in vitro and tumor growth in the xenograft mouse model. Furthermore, this anti-miR-21-mediated cell growth inhibition was associated with increased apoptosis and decreased cell proliferation, which could be in part owing to downregulation of the antiapoptotic Bcl-2 in anti-miR-21-treated tumor cells. Together, these results suggest that miR-21 functions as an oncogene and modulates tumorigenesis through regulation of genes such as bcl-2 and thus, it may serve as a novel therapeutic target.

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Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer.

Zhibin Hu, Xi Chen, Yang Zhao … (2010)

Recent findings that human serum contains stably expressed microRNA (miRNA) have revealed a great potential of serum miRNA signature as disease fingerprints to predict survival. We used genome-wide serum miRNA expression analysis to investigate the role of serum miRNA in predicting prognosis of non-small-cell lung cancer (NSCLC). To control disease heterogeneity, we used patients with stages I to IIIa lung adenocarcinoma and squamous cell carcinoma, who were treated with both operation and adjuvant chemotherapies. In the discovery stage, Solexa sequencing followed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between 30 patients with longer survival (alive and mean survival time, 49.54 months) and 30 patients with shorter survival matched by age, sex, and stage (dead and mean survival time, 9.54 months). The detected serum miRNAs then were validated in 243 patients (randomly classified into two subgroups: n = 120 for the training set, and n = 123 for the testing set). Eleven serum miRNAs were found to be altered more than five-fold by Solexa sequencing between longer-survival and shorter-survival groups, and levels of four miRNAs (ie, miR-486, miR-30d, miR-1 and miR-499) were significantly associated with overall survival. The four-miRNA signature also was consistently an independent predictor of overall survival for both training and testing samples. The four-miRNA signature from the serum may serve as a noninvasive predictor for the overall survival of NSCLC.

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Author and article information

Journal

Journal ID (nlm-ta): Cell Death Dis

Title: Cell Death & Disease

Publisher: Nature Publishing Group

ISSN (Electronic): 2041-4889

Publication date (Print): April 2011

Publication date (Electronic): 28 April 2011

Publication date PMC-release: 1 April 2011

Volume: 2

Issue: 4

Page: e151

Affiliations

[1 ]simpleIstituto Dermopatico dell'Immacolata-IRCCS , Roma, Italy

[2 ]simpleDipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara , Ferrara, Italy

Author notes

[* ]simpleIDI-IRCCS , Via dei Monti di Creta 104, 00167 Rome, Italy. Tel: +390666462432; Fax: +390666462430; E-mail: russo@ 123456idi.it

Article

Publisher Item ID: cddis201132

DOI: 10.1038/cddis.2011.32

PMC ID: 3122063

PubMed ID: 21525938

SO-VID: 8683bd1e-941d-4395-98b2-6029c4663d32

License:

This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

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

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Evolutionary Cell Biology

Most cited references 24

Origins and Mechanisms of miRNAs and siRNAs.

miR-21-mediated tumor growth.

Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer.

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