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首页> 外文期刊>Nucleic Acids Research >A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies
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A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies

机译：IGF1R基因位点内的新型反义长非编码RNA印在造血系统恶性肿瘤中。

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摘要

Dysregulation of the insulin-like growth factor type I receptor (IGF1R) has been implicated in the progression and therapeutic resistance of malignancies. In acute myeloid leukemia (AML) cells, IGF1R is one of the most abundantly phosphorylated receptor tyrosine kinases, promoting cell growth through the PI3K/Akt signaling pathway. However, little is known regarding the molecular mechanisms underlying IGF1R gene dysregulation in cancer. We discovered a novel intragenic long noncoding RNA (lncRNA) within theIGF1R locus, namedIRAIN, which is transcribed in an antisense direction from an intronic promoter. The IRAIN lncRNA was expressed exclusively from the paternal allele, with the maternal counterpart being silenced. Using both reverse transcription-associated trap and chromatin conformation capture assays, we demonstrate that this lncRNA interacts with chromatin DNA and is involved in the formation of an intrachromosomal enhancer/promoter loop. Knockdown of IRAIN lncRNA with shRNA abolishes this intrachromosomal interaction. In addition, IRAIN was downregulated both in leukemia cell lines and in blood obtained from high-risk AML patients. These data identify IRAIN as a new imprinted lncRNA that is involved in long-range DNA interactions.
机译：I型胰岛素样生长因子受体（IGF1R）的失调与恶性肿瘤的进展和治疗抵抗有关。在急性粒细胞白血病（AML）细胞中，IGF1R是磷酸化受体酪氨酸激酶最丰富的一种，可通过PI3K / Akt信号通路促进细胞生长。然而，关于癌症中IGF1R基因失调的分子机制知之甚少。我们在IGF1R基因座中发现了一个新的基因内长非编码RNA（lncRNA），名为IRAIN，它是从内含子启动子以反义方向转录的。 IRAIN lncRNA仅从父本等位基因表达，而母本对应基因被沉默。使用逆转录相关的陷阱和染色质构象捕获测定，我们证明了该lncRNA与染色质DNA相互作用，并参与了染色体内增强子/启动子环的形成。用shRNA敲除IRAIN lncRNA可消除这种染色体内相互作用。另外，从高危AML患者获得的白血病细胞系和血液中的IRAIN均被下调。这些数据将IRAIN鉴定为一种新的印记的lncRNA，涉及长距离DNA相互作用。

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