title: MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Sèzary syndrome patients.
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.
authors.affiliation: Center of Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kohnken
authors.affiliation: Center of Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Karthik M
authors.initials: KM
authors.lastname: Kodigepalli
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA; Division of Dermatology, Department of Internal Medicine, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Anjali
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Porcu
authors.affiliation: Center of Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, 43210, USA. Electronic address: wu.840@osu.edu.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D000076106:SAM Domain and HD Domain-Containing Protein 1; D012751:Sezary Syndrome / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: Cutaneous T-cell lymphoma; MicroRNA; SAMHD1; Sèzary syndrome