miR-223 is repressed and correlates with inferior clinical features in mantle cell lymphoma through targeting SOX11

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 G(0)/G(1) 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. 2018 ISEH Society for Hematology and Stem Cells. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.