title: A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies.
abstract: 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.
authors.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.
authors.forename: Jingnan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China jifan@stanford.edu jifanhu@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Sun
authors.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.
authors.forename: Dehai
authors.initials: D
authors.lastname: Yu
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wen
authors.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.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China.
authors.forename: Jiuwei
authors.initials: J
authors.lastname: Cui
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Wang
authors.affiliation: Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA jifan@stanford.edu jifanhu@126.com.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hoffman
authors.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 jifan@stanford.edu jifanhu@126.com.
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
mesh_terms: D000483:Alleles; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D018392:Genomic Imprinting; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics*
chemical_list: D002843:Chromatin; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D004247:DNA; D017526:Receptor, IGF Type 1
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