Genome-wide analysis of aberrantly expressed lncRNAs and miRNAs with associated co-expression and ceRNA networks in β-thalassemia and hereditary persistence of fetal hemoglobin.
Genome-wide analysis of aberrantly expressed lncRNAs and miRNAs with associated co-expression and ceRNA networks in β-thalassemia and hereditary persistence of fetal hemoglobin.
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对 β 地中海贫血和胎儿血红蛋白遗传持续性中异常表达的 lncRNA 和 miRNA 以及相关共表达和 ceRNA 网络进行全基因组分析
DOI：
10.18632/oncotarget.18263
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发表时间：
2017-07-25
期刊：
影响因子：
--
通讯作者：
He Y
中科院分区：
文献类型：
--
作者：
Lai K;Jia S;Yu S;Luo J;He Y
lncRNA 对血红蛋白疾病中胎儿血红蛋白 (HbF) 诱导的影响仍知之甚少。在本研究中，通过微阵列分析来分析具有遗传性胎儿血红蛋白持续性 (HPFH) 的个体、高 HbF 水平的 β-地中海贫血携带者和健康对照的 lncRNA、miRNA 和 mRNA。结果显示，与对照组相比，高HbF组中有862个lncRNA、568个mRNA和63个miRNA的异常表达。通过定量逆转录聚合酶链反应证实了 NR_001589、NR_120526、T315543、miR-486-3p、miR-19b-1-5p 和 miR-20a-3p 表达的改变，Spearman 相关系数显示与 HbF 呈显着正相关。 Gene Ontology 和京都基因与基因组百科全书通路富集分析表明，造血细胞谱系和细胞凋亡在 HbF 诱导过程中失调最为显着。我们分析了 lncRNA 附近的编码基因，并构建了编码-非编码共表达网络。根据这些结果，lncRNA 可能通过激活 HBE1 和造血细胞谱系诱导分子的表达以及抑制凋亡诱导分子的表达来导致 HbF 水平升高。最后，通过构建竞争性内源RNA网络，我们发现6个lncRNA可以与miR-486-3p竞争性结合，导致HbF水平升高。总而言之，我们的研究结果为 HbF 诱导机制提供了新的见解，并有可能为重型 β 地中海贫血的治疗提供新靶标。
The implications of lncRNAs regarding fetal hemoglobin (HbF) induction in hemoglobin disorders remain poorly understood. In this study, microarray analysis was performed to profile lncRNAs, miRNAs and mRNAs in individuals with hereditary persistence of fetal hemoglobin (HPFH), β-thalassemia carriers with high HbF levels and healthy controls. The results show aberrant expression of 862 lncRNAs, 568 mRNAs and 63 miRNAs in the high-HbF group compared with the control group. Altered NR_001589, NR_120526, T315543, miR-486-3p, miR-19b-1-5p and miR-20a-3p expression was confirmed by quantitative reverse transcription-polymerase chain reaction, and Spearman correlation coefficients revealed significant positive correlations with HbF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed the hematopoietic cell lineage and apoptosis to be most significantly dysregulated in HbF induction. We analyzed coding genes near the lncRNAs and constructed a coding-noncoding co-expression network. Based on the results, lncRNAs likely contribute to increased HbF levels by activating expression of HBE1 and hematopoietic cell lineage-inducible molecules and by inhibiting that of apoptosis-inducible molecules. Finally, through construction of a competing endogenous RNA network, we found that 6 lncRNAs could bind competitively with miR-486-3p, resulting in increased HbF levels. Taken together, our findings provide new insights into the mechanisms of HbF induction and potentially provide new targets for the treatment of β-thalassemia major.
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影响因子：
64.8
作者：
Venkatraman, Aparna;He, Xi C.;Thorvaldsen, Joanne L.;Sugimura, Ryohichi;Perry, John M.;Tao, Fang;Zhao, Meng;Christenson, Matthew K.;Sanchez, Rebeca;Yu, Jaclyn Y.;Peng, Lai;Haug, Jeffrey S.;Paulson, Ariel;Li, Hua;Zhong, Xiao-bo;Clemens, Thomas L.;Bartolomei, Marisa S.;Li, Linheng
通讯作者：
Li, Linheng
影响因子：
10.5
作者：
Hu, Wenqian;Yuan, Bingbing;Lodish, Harvey F.
通讯作者：
Lodish, Harvey F.
影响因子：
20.3
作者：
Walker, Aisha L.;Steward, Shirley;Ware, Russell E.
通讯作者：
Ware, Russell E.
影响因子：
3.7
作者：
Lulli V;Romania P;Morsilli O;Cianciulli P;Gabbianelli M;Testa U;Giuliani A;Marziali G
通讯作者：
Marziali G
DOI：
10.3324/haematol.2011.051730
发表时间：
2012-02-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Bissels, Ute;Bosio, Andreas;Wagner, Wolfgang
通讯作者：
Wagner, Wolfgang