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

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• 作者：Rebecca Kohnken^a ; Karthik M. Kodigepalli^a ; Anjali Mishra^b ; ^c ; Pierluigi Porcu^b ; ^d ; Li Wu^a ; ^b ; ^e ; ^{wu.840@osu.edu}
• 关键词：SAMHD1 ; sterile alpha motif and HD domain containing protein 1 ; CTCL ; cutaneous T-cell lymphoma ; SS ; Sé ; zary syndrome ; miR ; microRNA ; CLL ; chronic lymphocytic leukemia ; AGS ; Aicardi&ndash ; Goutierres syndrome
• 刊名：Leukemia Research
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：52
• 期：Complete
• 页码：58-66
• 全文大小：1881 K
• 卷排序：52

文摘

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.