Transcriptome profiling reveals the high incidence of hnRNPA1 exon 8 inclusion in chronic myeloid leukemia
Transcriptome profiling reveals the high incidence of hnRNPA1 exon 8 inclusion in chronic myeloid leukemia
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转录组分析揭示慢性粒细胞白血病中 hnRNPA1 外显子 8 包含的高发生率
DOI：
10.1016/j.jare.2020.04.016
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发表时间：
2020-07-01
影响因子：
10.7
通讯作者：
Wang, Xiao-Zhong
中科院分区：
文献类型：
--
作者：
Li, Shu-Qi;Liu, Jing;Wang, Xiao-Zhong
慢性粒细胞白血病 (CML) 是一种通过多步骤过程演变的恶性肿瘤。一些基因的选择性剪接与疾病的进展有关，但剪接谱的改变尚未见报道。外周血单核细胞 (PBMC) 样本的 RNA-seq 表征了 5 名 CML 慢性期 (CP) 和 5 名急变期 (BP) 患者以及 5 名健康对照者的差异表达和剪接转录本。全局剪接改变分析检测到 CML 和健康样本之间发生了 6474 个改变的剪接事件，包括许多先前报道的剪接变异，并显示出 BP 样本中更深刻的剪接失调改变。 CP 中差异剪接基因的功能聚类揭示了与细胞信号传导相关的首选富集，而剪接体途径在 BP 样本中表现最为过度。一个差异剪接的剪接体基因 hnRNPA1 显示出两种剪接亚型；包含外显子 8 的较长异构体优先在 BP 患者中表达，而排除外显子 8 的较短异构体则特异于健康对照。我们的研究结果表明，选择性剪接失调在 CML 从 CP 到 BP 的进展过程中发挥了核心作用，较长的 hnRNPA1 亚型可能代表 CML 的诊断标志物和治疗靶点。 (C) 2020 作者。由 Elsevier B.V. 代表开罗大学出版。这是一篇遵循 CC BY-NC-ND 许可证 (http://creativecommons.org/licenses/by-nc-nd/4.0/) 的开放获取文章。
Chronic myeloid leukemia (CML) is a malignancy that evolves through a multi-step process. Alternative splicing of several genes has been linked to the progression of the disease, but involvement of alternations in splicing profiles has not been reported. RNA-seq of peripheral blood mononuclear cell (PBMC) samples characterized the differentially expressed and spliced transcripts in five CML chronic phase (CP) and five blast phase (BP) patients, and five healthy controls. Global splicing alteration analysis detected 6474 altered splicing events altered between CML and healthy samples, including many of the previously reported splicing variants and showing a more profound altered splicing deregulation in BP samples. Functional clustering of differentially spliced genes in CP revealed a preferred enrichment relating to cell signaling, while the spliceosome pathway was most overrepresented in BP samples. One differentially spliced spliceosome gene hnRNPA1 showed two splice isoforms; the longer isoform contained exon 8 was preferentially expressed in the BP patients, and the short one excluding exon 8 was specific to healthy controls. Our findings suggested that alternative splicing deregulation played a central role during the progression of CML from CP to BP, and the longer isoform of hnRNPA1 might represent a diagnostic marker and therapeutic target for CML. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).