title: Aberrant allele-switch imprinting of a novel IGF1R intragenic antisense non-coding RNA in breast cancers.
abstract: The insulin-like growth factor type I receptor (IGF1R) is frequently dysregulated in breast cancers, yet the molecular mechanisms are unknown. A novel intragenic long non-coding RNA (lncRNA) IRAIN within the IGF1R locus has been recently identified in haematopoietic malignancies using RNA-guided chromatin conformation capture (R3C). In breast cancer tissues, we found that IRAIN lncRNA was transcribed from an intronic promoter in an antisense direction as compared to the IGF1R coding mRNA. Unlike the IGF1R coding RNA, this non-coding RNA was imprinted, with monoallelic expression from the paternal allele. In breast cancer tissues that were informative for single nucleotide polymorphism (SNP) rs8034564, there was an imbalanced expression of the two parental alleles, where the 'G' genotype was favorably imprinted over the 'A' genotype. In breast cancer patients, IRAIN was aberrantly imprinted in both tumours and peripheral blood leucocytes, exhibiting a pattern of allele-switch: the allele expressed in normal tissues was inactivated and the normally imprinted allele was expressed. Epigenetic analysis revealed that there was extensive DNA demethylation of CpG islands in the gene promoter. These data identify IRAIN lncRNA as a novel imprinted gene that is aberrantly regulated in breast cancer.
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Kang
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China; Stanford University Medical School, Stanford, CA 94305, 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.
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.
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, Stanford, CA 94305, USA.
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, Stanford, CA 94305, USA. Electronic address: Jifan@stanford.edu.
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China. Electronic address: drweili@yahoo.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D017526:Receptor, IGF Type 1
keywords: Allelic expression; Breast cancer; DNA methylation; Gene regulation; Genomic imprinting; IGF1R; IRAIN; Non-coding RNA