MiR-132-3p serves as a tumor suppressor in mantle cell lymphoma via directly targeting SOX11

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ORIGINAL ARTICLE

MiR-132-3p serves as a tumor suppressor in mantle cell lymphoma via directly targeting SOX11 Baoyu Wu 1 & Jingyu Li 1 & Han Wang 1 & Qian Wu 2 & Hui Liu 3 Received: 6 June 2019 / Accepted: 30 January 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Mantle cell lymphoma (MCL) is an uncommon type of non-Hodgkin’s lymphoma (NHL), comprising about 6% of NHL cases. SOX11 is a member of the group C of Sry-related high-mobility group (HMG) box (Sox) transcription factors, which is ubiquitously expressed in approximate 90% MCL cases. However, the underlying mechanisms of the SOX11 expression aberration are not fully unveiled. In the present study, we firstly observed that miR-132-3p was dramatically down-regulated in CD19+ lymphocytes isolated from peripheral blood mononuclear cells (PBMCs) of MCL patients. Subsequently, we found miR-132-3p exhibited potentials in clinical application, indicated by its negative association with high-risk clinical features. In terms of function, ectopic miR-132-3p aggravated cell apoptosis and arrested cell cycle in G0/G1, and then inhibited cell proliferation in vitro and tumor growth in vivo. Also, we identified miR-132-3p’s direct target, SOX11, in MCL cell lines, and loss-function of SOX11 blocked its inhibitory effect on cell proliferation in vitro. Collectively, our observations bring about a novel mechanism to explain the aberrant expression of SOX11 in MCL. Therefore, miR-132-3p may be a promising biomarker for the diagnosis of MCL. Keywords Mantle cell lymphoma (MCL) . miR-132-3p . SOX11

Introduction Mantle cell lymphoma (MCL) is one of the most aggressive lymphoid neoplasms manifested clinically by extensive tumor cells invading lymphoid tissues, bone marrow (BM), peripheral blood (PB), and extranodal sites (Balsas et al. 2017). In epidemiology, MCL is an uncommon type of non-Hodgkin’s lymphoma (NHL), comprising about 6% of NHL cases, with an annual incidence of 0.5 per 100,000 population in western countries (Skarbnik and Goy 2015; Cheah et al. 2016). The putative initiating oncogenic event of MCL is the t(11;14)(q13;q32) translocation, which finally leads to the constitutive overexpression of CCND1 to cause cell cycle * Hui Liu [email protected] 1

Department of Pathology, Xuzhou Children’s Hospital, Xuzhou Medical University, Xuzhou, Jiangsu, China

2

Department of Dermatology, Xuzhou Children’s Hospital, Xuzhou Medical University, Xuzhou, Jiangsu, China

3

Department of Pathology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China

deregulation in a cyclin-dependent kinases 4 and 6 (CDK4/6) dependent manner (Jares et al. 2012). However, CCND1-negative MCL was reported in 6 independent clinical cases; suggesting the overexpression of CCND1 in isolation is not sufficient to totally explain the pathogenesis of this disease (Fu et al. 2005; Cheah et al. 2016). Therefore, the etiology of MCL needs further investigation. SOX11 is a transcription factor involved in cardiac, neuronal, and other major developmental