LOC101928834，Wnt/β-catenin 信号通路中的一种新型 lncRNA，促进细胞增殖，并预测骨髓增生异常综合征的不良临床结局。

LOC101928834, a novel lncRNA in Wnt/β-catenin signaling pathway, promotes cell proliferation and predicts poor clinical outcome in myelodysplastic syndromes.

机构信息

Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.

Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.

出版信息

Clin Sci (Lond). 2020 Jun 12;134(11):1279-1293. doi: 10.1042/CS20200439.

DOI:10.1042/CS20200439

PMID:32463458

Abstract

Long non-coding RNAs (lncRNAs) play important roles in hematological malignancies. We have previously identified several differentially expressed lncRNAs in myelodysplastic syndromes (MDS) by microarray analysis. In the present study, we explored the regulatory circuitry, potential functions, clinical and prognostic relevance of these lncRNAs in MDS by developing a lncRNA regulation network. We identified a novel lncRNA, LOC101928834, which was significantly up-regulated in the bone marrow of patients with MDS and acute myeloid leukemia (AML). We further evaluated the clinical relevance of LOC101928834 in 89 MDS and 110 AML patients and found that higher level of LOC101928834 expression was associated with higher white blood cell count, higher blast percentage, the subtype of refractory cytopenia with excess blasts (RAEB) and shorter overall survival in MDS patients. Receiver operating characteristic (ROC) curve analysis showed that LOC101928834 expression could discriminate MDS-RAEB patients from control with an area under the receiver-operating curve (AUC) of 0.9048. Moreover, functional analysis showed that LOC101928834 promoted cell proliferation and cell cycle progression, and activated Wnt/β-catenin signaling pathway in vitro. In conclusion, LOC101928834 expression is correlated with clinical and biological features of MDS and may serve as a novel diagnostic and prognostic biomarker.

摘要

长链非编码 RNA（lncRNAs）在血液系统恶性肿瘤中发挥着重要作用。我们之前通过微阵列分析在骨髓增生异常综合征（MDS）中鉴定了几种差异表达的 lncRNA。在本研究中，我们通过开发 lncRNA 调控网络，探索了这些 lncRNA 在 MDS 中的调控回路、潜在功能、临床和预后相关性。我们鉴定了一种新型 lncRNA，LOC101928834，其在 MDS 和急性髓系白血病（AML）患者的骨髓中显著上调。我们进一步评估了 LOC101928834 在 89 例 MDS 和 110 例 AML 患者中的临床相关性，发现更高水平的 LOC101928834 表达与更高的白细胞计数、更高的原始细胞百分比、难治性血细胞减少伴原始细胞过多（RAEB）亚型以及 MDS 患者的总生存期更短相关。受试者工作特征（ROC）曲线分析显示，LOC101928834 表达可将 MDS-RAEB 患者与对照者区分开来，ROC 曲线下面积（AUC）为 0.9048。此外，功能分析表明，LOC101928834 在体外促进细胞增殖和细胞周期进程，并激活 Wnt/β-catenin 信号通路。总之，LOC101928834 的表达与 MDS 的临床和生物学特征相关，可能作为一种新的诊断和预后生物标志物。