A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies.
Bottom Line: 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.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.
Affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.Show MeSH
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Mentions: IGFIR is frequently overexpressed in both solid tumors and hematopoietic malignancies, participating in the regulation of cancer cell proliferation, survival, metabolism and metastasis. To address the mechanisms underlying the dysregulation of IGF1R in leukemia cells, we used a novel R3C method recently developed in our lab (Supplementary Figure S1) (22), and detected the presence of RNA molecules within the IGF1R promoter and intron 1, where the IGF1R mRNA is not transcribed. To characterize this novel RNA molecule, we designed a series of PCR primers covering the IGF1R promoter region and mapped its transcription in the IGF1R locus (Figure 1A). Using PCR, we detected the transcription of this noncoding RNA from the IGF1R promoter and intron 1 (Figure 1B, from C to H sites, lanes 3–8). No PCR products were detected further upstream (sites A, B; lanes 1–2) or the region near exon 2 (sites I, J; lanes 9–10).
Affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.