Long noncoding RNA FAM157C contributes to clonal proliferation in paroxysmal nocturnal hemoglobinuria.
Long noncoding RNA FAM157C contributes to clonal proliferation in paroxysmal nocturnal hemoglobinuria.
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DOI：
10.1007/s00277-022-05055-8
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发表时间：
2023-02
影响因子：
3.5
通讯作者：
Fu, Rong
中科院分区：
文献类型：
--
作者：
Wang, Honglei;Liu, Hui;Li, Liyan;Chen, Yingying;Liu, Zhaoyun;Li, Lijuan;Ding, Shaoxue;Ding, Kai;Fu, Rong
阵发性睡眠性血红蛋白尿症是一种罕见的造血干细胞克隆性疾病。长链非编码RNA（lncRNA）具有广泛的生物学功能，包括基因表达、细胞分化和增殖的调节，但它们在PNH中的作用尚不清楚。对35例PNH患者的CD 59-和CD 59+粒细胞和单核细胞进行了分选。对5例PNH患者进行高通量测序分析，鉴定差异表达的lncRNA和mRNA。选择至少3例患者中每百万定位片段外显子模型（FPKM）中每个外显子酶的片段数（FPKM）> 10的mRNA，并进行实验以鉴定其上游调控lncRNA。通过qRT-PCR验证所选mRNA和lncRNA的表达，并分析这些表达模式与其他30例PNH患者的临床数据的相关性。然后，在PIGA-KO-THP-1细胞系中研究lncRNA的功能。转录分析显示742个上调和1376个下调的lncRNA和3276个上调和213个下调的mRNA。在深入筛选后，分析与NF-κB通路相关的8个高表达mRNA以确定共表达模式。LINC 01002、FAM 157 C、CTD-2530H12.2、XCRN-064331和XCRN-106677与8种mRNA相关。在通过qRT PCR测量30名PNH患者中这些分子的表达后，证实lncRNA FAM 157 C在PNH克隆中上调，并且其表达水平与LDH水平和CD 59 −颗粒和单核细胞比率呈正相关。FAM 157 C基因敲除后，细胞阻滞于G 0/G1期和S期，凋亡率增加，细胞增殖能力下降。LncRNA FAM 157 C被证明促进PNH克隆增殖，这是首次探讨lncRNA在PNH中的作用的研究。在线版本包含补充材料，可通过10.1007/s 00277 -022-05055-8获得。
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease of hematopoietic stem cells (HSCs). Long noncoding RNAs (lncRNAs) perform a wide range of biological functions, including the regulation of gene expression, cell differentiation, and proliferation, but their role in PNH remains unclear. CD59− and CD59+ granulocytes and monocytes from 35 PNH patients were sorted. High-throughput sequencing was analyzed in 5 PNH patients, and differentially expressed lncRNAs and mRNAs were identified. The mRNAs with fragments per kilobase of exon model per million mapped fragments (FPKM) > 10 in at least 3 patients were selected, and experiments were performed to identify their upstream regulatory lncRNAs. The expression of selected mRNAs and lncRNAs was verified by qRT‒PCR, and the correlation of these expression patterns with clinical data from other 30 PNH patients was analyzed. Then, the functions of the lncRNAs were studied in the PIGA-KO-THP-1 cell line. Transcription analysis revealed 742 upregulated and 1376 downregulated lncRNAs and 3276 upregulated and 213 downregulated mRNAs. After deep screening, 8 highly expressed mRNAs that were related to the NF-κB pathway were analyzed to determine coexpression patterns. LINC01002, FAM157C, CTD-2530H12.2, XLOC-064331 and XLOC-106677 were correlated with the 8 mRNAs. After measuring the expression of these molecules in 30 PNH patients by qRT‒PCR, lncRNA FAM157C was verified to be upregulated in the PNH clone, and its expression levels were positively correlated with the LDH levels and CD59− granulated and monocyte cell ratios. After knockdown of the FAM157C gene in the PIGA-KO-THP-1 cell line, we found that the cells were arrested in the G0/G1 phase and S phase, the apoptosis rate increased, and the cell proliferation decreased. LncRNA FAM157C was proven to promote PNH clone proliferation, and this is the first study to explore the role of lncRNAs in PNH. The online version contains supplementary material available at 10.1007/s00277-022-05055-8.
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DOI：
10.1038/nrdp.2017.28
发表时间：
2017-05-18
期刊：
Nature reviews. Disease primers
影响因子：
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作者：
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通讯作者：
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DOI：
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