Wang Weimin, Lyu Chunhui, Wang Fei, Wang Congcong, Wu Feifei, Li Xue, Gan Silin
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Genet. 2021 Jul 6;12:656042. doi: 10.3389/fgene.2021.656042. eCollection 2021.
Acute lymphoblastic leukemia (ALL) is a malignant disease most commonly diagnosed in adolescents and young adults. This study aimed to explore potential signatures and their functions for ALL.
Differentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified for ALL from The Cancer Genome Atlas (TCGA) and normal control from Genotype-Tissue Expression (GTEx). DElncRNA-microRNA (miRNA) and miRNA-DEmRNA pairs were predicted using online databases. Then, a competing endogenous RNA (ceRNA) network was constructed. Functional enrichment analysis of DEmRNAs in the ceRNA network was performed. Protein-protein interaction (PPI) network was then constructed. Hub genes were identified. DElncRNAs in the ceRNA network were validated using Real-time qPCR.
A total of 2,903 up- and 3,228 downregulated mRNAs and 469 up- and 286 downregulated lncRNAs were identified for ALL. A ceRNA network was constructed for ALL, consisting of 845 lncRNA-miRNA and 395 miRNA-mRNA pairs. These DEmRNAs in the ceRNA network were mainly enriched in ALL-related biological processes and pathways. Ten hub genes were identified, including SMAD3, SMAD7, SMAD5, ZFYVE9, FKBP1A, FZD6, FZD7, LRP6, WNT1, and SFRP1. According to Real-time qPCR, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were significantly upregulated in ALL bone marrow samples compared to normal samples.
Our results showed the lncRNA expression profiles and constructed ceRNA network in ALL. Furthermore, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were identified. These results could provide a novel insight into the study of ALL.
急性淋巴细胞白血病（ALL）是一种最常见于青少年和年轻成年人的恶性疾病。本研究旨在探索ALL的潜在特征及其功能。
从癌症基因组图谱（TCGA）中鉴定ALL的差异表达mRNA（DEmRNAs）和差异表达长链非编码RNA（DElncRNAs），并从基因型组织表达（GTEx）中获取正常对照。使用在线数据库预测DElncRNA-微小RNA（miRNA）和miRNA-DEmRNA对。然后，构建竞争性内源RNA（ceRNA）网络。对ceRNA网络中的DEmRNAs进行功能富集分析。接着构建蛋白质-蛋白质相互作用（PPI）网络。鉴定枢纽基因。使用实时定量PCR验证ceRNA网络中的DElncRNAs。
共鉴定出ALL中2903个上调和3228个下调的mRNA以及469个上调和286个下调的lncRNA。构建了ALL的ceRNA网络，由845个lncRNA-miRNA对和395个miRNA-mRNA对组成。ceRNA网络中的这些DEmRNAs主要富集于ALL相关的生物学过程和通路。鉴定出10个枢纽基因，包括SMAD3、SMAD7、SMAD5、ZFYVE9、FKBP1A、FZD6、FZD7、LRP6、WNT1和SFRP1。根据实时定量PCR，与正常样本相比，ALL骨髓样本中包括ATP11A-AS1、ITPK1-AS1、ANO1-AS2、CRNDE、MALAT1、CACNA1C-IT3、PWRN1和WT1-AS在内的8个lncRNA显著上调。
我们的结果显示了ALL中的lncRNA表达谱并构建了ceRNA网络。此外，鉴定出包括ATP11A-AS1、ITPK1-AS1、ANO1-AS2、CRNDE、MALAT1、CACNA1C-IT3、PWRN1和WT1-AS在内的8个lncRNA。这些结果可为ALL的研究提供新的见解。
