MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Sèzary syndrome patients

Rebecca Kohnken; Karthik M Kodigepalli; Anjali Mishra; Pierluigi Porcu; Li Wu

doi:10.1016/j.leukres.2016.11.010

Back

MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Sèzary syndrome patients

Journal article

Open access

Peer reviewed

MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Sèzary syndrome patients

Rebecca Kohnken, Karthik M Kodigepalli, Anjali Mishra, Pierluigi Porcu and Li Wu

Leukemia research, Vol.52, pp.58-66

01/2017

DOI: 10.1016/j.leukres.2016.11.010

PMCID: PMC5195900

PMID: 27889686

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/5195900View

Open Access

Abstract

Sézary syndrome (SS) is a rare subtype of cutaneous T-cell lymphoma (CTCL) that is characterized by aggressive spread of neoplastic CD4+ T-cells from the skin into the bloodstream with metastasis to visceral organs. The deoxynucleoside triphosphohydrolase SAMHD1 is highly expressed in normal CD4+ T-cells, while its expression is down-regulated in CD4+ T-cells from SS patients. MicroRNA (miR) dysregulation is an important epigenetic mechanism in the pathogenesis and progression of SS. MiR-181 has been shown to inhibit SAMHD1 expression in cell lines and was identified as an important prognostic biomarker in CTCL. However, whether SAMHD1 is down-regulated by miR-181 in primary CD4+ T-cells of SS patients is unknown. Compared to normal CD4+ T-cells, SAMHD1 protein expression is significantly reduced in transformed CD4+ T-cell lines and CD4+ T-cells from SS patients, which inversely correlates with increased miR-181 levels in these cells. Over-expression of miR-181b in primary CD4+ T-cells from healthy donors significantly decreased SAMHD1 protein level, but not mRNA level. In contrast, inhibition of miR-181 in a CD4+ T-cell line significantly increased the level of SAMHD1 protein expression. Our results demonstrate that miR-181 is an important regulator of SAMHD1 protein expression in neoplastic CD4+ T-cells, likely through a mechanism of translational inhibition.

MicroRNA

SAMHD1

Sèzary syndrome

Cutaneous T-cell lymphoma

Details

Title: Subtitle: MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Sèzary syndrome patients
Creators: Rebecca Kohnken - Center of Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA
Karthik M Kodigepalli - Center of Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA
Anjali Mishra - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
Pierluigi Porcu - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
Li Wu - Center of Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA
Resource Type: Journal article
Publication Details: Leukemia research, Vol.52, pp.58-66
DOI: 10.1016/j.leukres.2016.11.010
PMID: 27889686
PMCID: PMC5195900
NLM abbreviation: Leuk Res
ISSN: 0145-2126
eISSN: 1873-5835
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100000002, name: NIH, award: CA181997, OD010429, AI074658, AI120209, AI127667; name: Public Health Preparedness for Infectious Diseases Program of the Ohio State University
Language: English
Date published: 01/2017
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001228102771

Metrics

29 Record Views

21 Times Cited - Web of Science

See more details