Abstract
<div>Abstract<p><b>Purpose:</b> Deregulation of microRNA (miRNA) has been extensively investigated in both Hodgkin and non-Hodgkin lymphomas (NHL); however, little is known about the roles of miRNAs in T-cell lymphoblastic lymphoma (T-LBL). The aim of the present study was to investigate the potential roles of miR-374b in the development and treatment of T-LBL.</p><p><b>Experimental Design:</b> MiRCURY LNA array was used to generate a miRNA-expressing profile. Real-time quantitative PCR and immunohistochemistry (IHC) were applied to detect the expression of miR-374b, AKT1, and Wnt16 in T-LBL samples. The dual-luciferase reporter assay was conducted to confirm target associations of miR-374b. The tumor-suppressive effect of miR-374b was determined by both <i>in vitro</i> and <i>in vivo</i> studies.</p><p><b>Results:</b> The expression of 380 miRNAs was evaluated in five human T-LBL tissues and five infantile thymus samples by microRNA microarrays. Downregulation of miR-374b was frequently detected in primary T-LBL tissues, which was significantly associated with worse overall survival and increased risk of recurrence of the 58 patients enrolled in this study. miR-374b suppressed T-LBL cell proliferation <i>in vitro</i> and <i>in vivo</i> and sensitized cells to serum starvation- and chemotherapeutic agent-induced apoptosis. Furthermore, we characterized two AKT pathway–associated molecules, AKT1 and Wnt16, as direct targets of miR-374b. Consistently, in T-LBL patient tissues, AKT1 and Wnt16 expression was inversely correlated with miR-374b levels, and was an independent predictor of recurrence and survival.</p><p><b>Conclusions:</b> Our data highlight the molecular etiology and clinical significance of miR-374b in T-LBL. Targeting miR-374b may represent a new therapeutic strategy to improve therapy and survival for T-LBL patients. <i>Clin Cancer Res; 21(21); 4881–91. ©2015 AACR</i>.</p></div>
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