Mantle cell lymphoma (MCL) is an aggressive lymphoid malignancy characterized by cytogenetic aberration of t(11;14), although it is not the prerequisite. Until now, the pathogenesis of MCL has not been fully interpreted. Our current study showed that microRNA (miR)-223 was downregulated in purified CD19+ lymphocytes from MCL patients (n = 21) compared with that of healthy donors (n = 20). In addition, patients with a high-risk Mantle Cell Lymphoma International Prognostic Index (MIPI) score, elevated lactate dehydrogenase, and Eastern Cooperative Oncology Group performance status >2 were more likely to have much lower miR-223 expression. Furthermore, low miR-223 expression predicted inferior overall survival regardless of treatment in our cohort of 21. To explore the role of miR-223 in MCL, we constructed an ectopic miR-223 MCL cell line and revealed that miR-223 inhibited cell proliferation and promoted G0/G1 accumulation and cell apoptosis. A database search showed that SOX11, a crucial transcription factor in MCL, is the putative target of miR-223. In support of this, we observed a much lower level of SOX11 protein in miR-223-overexpressing cells than in parental cells. Further, the luciferase reporter assay confirmed that miR-223 at the posttranscriptional level suppressed the wild-type 3'-untranslated region of SOX11 but not the mutated one. Finally, miR-223 was found to be negatively correlated with the mRNA level of SOX11 in clinical samples. Our work demonstrates for the first time that miR-223 is repressed and correlated with high-risk clinical features in MCL, which provides a potential molecule to target to optimize MCL management.
Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.