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miR-132-3p 通过直接靶向 SOX11 在套细胞淋巴瘤中作为肿瘤抑制因子。

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

机构信息

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.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2020 Nov;393(11):2197-2208. doi: 10.1007/s00210-020-01834-0. Epub 2020 Feb 10.

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.

摘要

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。

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