Department of Pathology, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Department of Dermatology, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Nov;393(11):2197-2208. doi: 10.1007/s00210-020-01834-0. Epub 2020 Feb 10.
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.
套细胞淋巴瘤（MCL）是一种罕见的非霍奇金淋巴瘤（NHL），约占 NHL 病例的 6%。SOX11 是 Sry 相关高迁移率族（HMG）盒（Sox）转录因子 C 组的成员，在大约 90%的 MCL 病例中广泛表达。然而，SOX11 表达异常的潜在机制尚未完全揭示。在本研究中，我们首先观察到 miR-132-3p 在 MCL 患者外周血单个核细胞（PBMCs）分离的 CD19 淋巴细胞中显著下调。随后，我们发现 miR-132-3p 具有临床应用潜力，其与高危临床特征呈负相关。就功能而言，外源性 miR-132-3p 加重了细胞凋亡，使细胞周期停滞在 G0/G1 期，从而抑制了体外细胞增殖和体内肿瘤生长。此外，我们在 MCL 细胞系中鉴定了 miR-132-3p 的直接靶标 SOX11，SOX11 的功能丧失阻断了其对体外细胞增殖的抑制作用。总之，我们的观察结果为解释 MCL 中 SOX11 的异常表达提供了一种新的机制。因此，miR-132-3p 可能是 MCL 诊断的有前途的生物标志物。
