A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies.
A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies.
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IGF1R基因座内的一种新型反义长非编码RNA被印记于造血系统恶性肿瘤中
DOI：
10.1093/nar/gku549
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发表时间：
2014-09
影响因子：
14.9
通讯作者：
Hu JF
中科院分区：
文献类型：
--
作者：
Sun J;Li W;Sun Y;Yu D;Wen X;Wang H;Cui J;Wang G;Hoffman AR;Hu JF
胰岛素样生长因子I型受体(IGF1R)的失调与恶性肿瘤的进展和治疗耐药有关。在急性髓系白血病(AML)细胞中，IGF1R是磷酸化程度最高的受体酪氨酸激酶之一，通过PI3K/Akt信号通路促进细胞生长。然而，关于IGF1R基因在癌症中调控失调的分子机制还知之甚少。我们在IGF1R基因座上发现了一个新的基因内长非编码RNA(LncRNA)，命名为IRAIN，它是从内含子启动子反义转录而来的。IRAIN lncRNA只在父亲的等位基因中表达，而母亲的等位基因被沉默。利用逆转录相关的TRAP和染色质构象捕获分析，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。此外，IRAIN在白血病细胞系和高危AML患者的血液中表达下调。这些数据证明IRAIN是一种新的印迹lncRNA，参与了远程DNA相互作用。
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 the IGF1R locus, named IRAIN, 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.
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影响因子：
11.2
作者：
Wahner Hendrickson AE;Haluska P;Schneider PA;Loegering DA;Peterson KL;Attar R;Smith BD;Erlichman C;Gottardis M;Karp JE;Carboni JM;Kaufmann SH
通讯作者：
Kaufmann SH
影响因子：
4.8
作者：
Hu, JF;Vu, TH;Hoffman, AR
通讯作者：
Hoffman, AR
影响因子：
4
作者：
Chu, Yongjun;Kalantari, Roya;Corey, David R.
通讯作者：
Corey, David R.
影响因子：
9.8
作者：
Ferrai C;Xie SQ;Luraghi P;Munari D;Ramirez F;Branco MR;Pombo A;Crippa MP
通讯作者：
Crippa MP
影响因子：
56.9
作者：
Latos, Paulina A.;Pauler, Florian M.;Barlow, Denise P.
通讯作者：
Barlow, Denise P.