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关注新诊断多发性骨髓瘤中的长链非编码RNA失调。

Focusing on long non-coding RNA dysregulation in newly diagnosed multiple myeloma.

作者信息

Shen Ying, Feng Yuandong, Chen Hongli, Huang Lingjuan, Wang Fangxia, Bai Ju, Yang Yun, Wang Jianli, Zhao Wanhong, Jia Yachun, Peng Yan, Lei Xiaoru, He Aili

机构信息

Department of Hematology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Department of Geriatrics, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China.

出版信息

Life Sci. 2018 Mar 1;196:133-142. doi: 10.1016/j.lfs.2018.01.025. Epub 2018 Feb 3.

Abstract

AIMS

Multiple myeloma (MM) is an incurable hematological cancer with a higher rate of relapse. Alterations in the function of long non-coding RNAs (lncRNAs) promote the progression and metastasis of cancer. We carry out this study to explore the expression profile of differently expressed lncRNAs in newly diagnosed MM.

MAIN METHODS

The Bone marrows we analyzed were obtained from five MM and five IDA patients (serving as controls). Arraystar Human LncRNA Array V4.0 was used to profile expression of lncRNAs and mRNAs. Gene ontology (GO) and pathway analysis were utilized to understand the biological roles of differently expressed genes, while Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for constructing the lncRNA-mRNA co-expression network. Quantitative polymerase chain reaction (qRT-PCR) was performed to confirm the expressions of dysregulated lncRNAs.

KEY FINDINGS

Bioinformatic analysis of the lncRNA expression identified >3000 dysregulated lncRNAs (difference ≥ 2-fold) in MM samples. GO and pathway analysis revealed that ECM-receptor and cell cycle pathway-related genes were significantly associated with MM. Four dysregulated lncRNAs were confirmed by qRT-PCR. Among them, the expression of ST3GAL6-AS1, LAMA5-AS1and RP11-175D17.3wereassociated with stage and risk status of MM. On the basis of GEO public database analysis, LAMA5-AS1 was related with an overall survival rate of MM patients.

SIGNIFICANCE

These results reveal the feasible functions of lncRNAs in pathogenesis of MM. Further studies are required to explore whether these lncRNAs could serve as candidate therapeutic targets and new molecular biomarkers for MM.

摘要

目的

多发性骨髓瘤(MM)是一种无法治愈的血液系统癌症,复发率较高。长链非编码RNA(lncRNA)功能的改变会促进癌症的进展和转移。我们开展本研究以探索新诊断MM中差异表达lncRNA的表达谱。

主要方法

我们分析的骨髓样本来自5例MM患者和5例缺铁性贫血(IDA)患者(作为对照)。使用Arraystar人类lncRNA芯片V4.0分析lncRNA和mRNA的表达。利用基因本体(GO)和通路分析来了解差异表达基因的生物学作用,同时使用注释、可视化和综合发现数据库(DAVID)构建lncRNA - mRNA共表达网络。通过定量聚合酶链反应(qRT - PCR)来确认失调lncRNA的表达。

主要发现

对lncRNA表达的生物信息学分析在MM样本中鉴定出>3000个失调的lncRNA(差异≥2倍)。GO和通路分析显示,细胞外基质受体和细胞周期通路相关基因与MM显著相关。通过qRT - PCR确认了4个失调的lncRNA。其中,ST3GAL6 - AS1、LAMA5 - AS1和RP11 - 175D17.3的表达与MM的分期和风险状态相关。基于GEO公共数据库分析,LAMA5 - AS1与MM患者的总生存率相关。

意义

这些结果揭示了lncRNA在MM发病机制中的可行功能。需要进一步研究来探索这些lncRNA是否可作为MM的候选治疗靶点和新的分子生物标志物。

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