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异常的 NEAT1_1 表达可能是弥漫性大 B 细胞淋巴瘤不良预后的预测标志物。

Aberrant NEAT1_1 expression may be a predictive marker of poor prognosis in diffuse large B cell lymphoma.

机构信息

Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.

Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

出版信息

Cancer Biomark. 2018;23(2):157-164. doi: 10.3233/CBM-160221.

DOI:10.3233/CBM-160221
PMID:30175971
Abstract

BACKGROUND

Many studies have demonstrated that the long non-coding RNA (lncRNA), NEAT1_1, plays critical roles in various human tumor entities and is related to the survival of patients with malignancies. However, the role of NEAT1_1 in diffuse large B cell lymphoma (DLBCL) remains unclear. The aim of this study was to investigate the role of NEAT1_1 in DLBCL.

METHODS

The expression of NEAT1_1 was evaluated in paraffin-embedded tissues from 64 DLBCL patients and 15 lymphnoditis patients using the ISH method. The correlations between the expression levels of NEAT1_1 and clinical-pathological features and patients' survival were also analyzed. After knocking down NEAT1_1 using shRNA in the DLBCL cell lines OCI-Ly1 and SUDHL-4, cell viability, apoptosis and migration were assessed by performing CCK8 assays, annexin V-FITC/PI double staining assays and migration filter assays, respectively.

RESULTS

NEAT1_1 expression was increased in DLBCL tissue compared to lymphnoditis tissue samples (P< 0.001). The NEAT1_1 level was positively related to stage (P= 0.031), IPI (P= 0.017), extranodal site involvement (P= 0.042) and drug response (P= 0.040). Kaplan-Meier analysis showed that high expression levels of NEAT1_1 were correlated with a poor prognosis in DLBCL patients. After shRNA-NEAT1_1 was transfected into OCI-Ly1 and SUDHL-4 for 24 h, the NEAT1_1 level decreased to approximately one-third the level of the control. Moreover, the viability and migration ability of the DLBCL cell lines were significantly suppressed. shRNA-NEAT1_1 induced apoptosis in both DLBCL cell lines.

CONCLUSIONS

Our results showed that NEAT1_1 plays an oncogenic role in DLBCL. NEAT1_1 expression may serve as a predictive marker for DLBCL patients.

摘要

背景

许多研究表明,长链非编码 RNA(lncRNA),NEAT1_1,在各种人类肿瘤实体中发挥关键作用,与恶性肿瘤患者的生存有关。然而,NEAT1_1 在弥漫性大 B 细胞淋巴瘤(DLBCL)中的作用尚不清楚。本研究旨在探讨 NEAT1_1 在 DLBCL 中的作用。

方法

采用原位杂交法检测 64 例 DLBCL 患者和 15 例淋巴结炎患者石蜡包埋组织中 NEAT1_1 的表达,并分析其与临床病理特征及患者生存的关系。采用 shRNA 敲低 DLBCL 细胞系 OCI-Ly1 和 SUDHL-4 中的 NEAT1_1 后,通过 CCK8 检测、Annexin V-FITC/PI 双染法检测和迁移滤器检测分别评估细胞活力、细胞凋亡和细胞迁移。

结果

与淋巴结炎组织样本相比,DLBCL 组织中 NEAT1_1 的表达增加(P<0.001)。NEAT1_1 水平与分期(P=0.031)、IPI(P=0.017)、结外部位受累(P=0.042)和药物反应(P=0.040)呈正相关。Kaplan-Meier 分析显示,NEAT1_1 高表达与 DLBCL 患者预后不良相关。shRNA-NEAT1_1 转染 OCI-Ly1 和 SUDHL-4 24 h 后,NEAT1_1 水平降至对照组的约三分之一。此外,DLBCL 细胞系的活力和迁移能力明显受到抑制。shRNA-NEAT1_1 诱导了两种 DLBCL 细胞系的凋亡。

结论

我们的研究结果表明,NEAT1_1 在 DLBCL 中发挥致癌作用。NEAT1_1 的表达可能成为预测 DLBCL 患者的一个标志物。

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