Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers.
The human chromosome region 11p15.5 contains a number of maternally and paternally imprinted genes, and the LIT1/KCNQ1OT1 locus acts as an imprinting center in the proximal domain of 11p15.5. Loss of imprinting (LOI) of LIT1 and its correlation with methylation status at a differentially methylated region, the KvDMR1, were investigated in 69 colorectal cancer tissue specimens. LIT1 expression profiles were also examined by RNA-fluorescence in situ hybridization in 13 colorectal cancer cell lines. In 69 colorectal cancer tissue specimens, LOI of LIT1 was observed in nine of the 17 (53%) informative cases. Moreover, LOI of LIT1 was only observed in tumor samples. In the cell lines, methylation status at the KvDMR1 correlated well with LIT1 expression profiles. Loss of expression of LIT1 also correlated with enrichment of H3 lysine 9 (H3-K9) dimethylation and reduction of H3 lysine 4 (H3-K4) dimethylation. Thus, LIT1 expression appears to be controlled by epigenetic modifications at the KvDMR1, although CDKN1C expression, which is considered to be controlled by LIT1, was not associated with epigenetic status at the KvDMR1 in some colorectal cancer cell lines. Therefore, these findings suggest that LOI of LIT1 via epigenetic disruption plays an important role in colorectal carcinogenesis, but it is not necessarily associated with CDKN1C expression.
Nakano
Seiji
S
Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, 86 Nishimachi, Yonago, Tottori 683-8503, Japan.
Murakami
Kazuhiro
K
Meguro
Makiko
M
Soejima
Hidenobu
H
Higashimoto
Ken
K
Urano
Takeshi
T
Kugoh
Hiroyuki
H
Mukai
Tsunehiro
T
Ikeguchi
Masahide
M
Oshimura
Mitsuo
M
D047369:Chromatin Immunoprecipitation; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007335:Insulin-Like Growth Factor II; D008565:Membrane Proteins / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D011506:Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D014407:Tumor Cells, Cultured
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; C485621:KCNQ1OT1 long non-coding RNA, human; D008565:Membrane Proteins; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II