title: Regulation of functional KCNQ1OT1 lncRNA by β-catenin.
abstract: Long noncoding RNAs (lncRNAs) have been implicated in many biological processes through epigenetic mechanisms. We previously reported that KCNQ1OT1, an imprinted antisense lncRNA in the human KCNQ1 locus on chromosome 11p15.5, is involved in cis-limited silencing within an imprinted KCNQ1 cluster. Furthermore, aberration of KCNQ1OT1 transcription was observed with a high frequency in colorectal cancers. However, the molecular mechanism of the transcriptional regulation and the functional role of KCNQ1OT1 in colorectal cancer remain unclear. Here, we show that the KCNQ1OT1 transcriptional level was significantly increased in human colorectal cancer cells in which β-catenin was excessively accumulated in the nucleus. Additionally, overexpression of β-catenin resulted in an increase in KCNQ1OT1 lncRNA-coated territory. On the other hand, knockdown of β-catenin resulted in significant decrease of KCNQ1OT1 lncRNA-coated territory and an increase in the mRNA expression of the SLC22A18 and PHLDA2 genes that are regulated by KCNQ1OT1. We showed that β-catenin can promote KCNQ1OT1 transcription through direct binding to the KCNQ1OT1 promoter. Our evidence indicates that β-catenin signaling may contribute to development of colorectal cancer by functioning as a novel lncRNA regulatory factor via direct targeting of KCNQ1OT1.
authors: Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503, Japan.
authors: Naohiro
authors: N
authors: Sunamura
authors: Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503, Japan.
authors: Takahito
authors: T
authors: Ohira
authors: Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503, Japan.
authors: Miki
authors: M
authors: Kataoka
authors: Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503, Japan.
authors: Daigo
authors: D
authors: Inaoka
authors: Department of Evolutionary Studies of Biosystems Science, School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies), Shonan Village, Hayama, Kanagawa 240-0193, Japan.
authors: Hideyuki
authors: H
authors: Tanabe
authors: Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503, Japan.
authors: Yuji
authors: Y
authors: Nakayama
authors: Chromosome Engineering Research Center, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503, Japan.
authors: Mitsuo
authors: M
authors: Oshimura
authors: Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503, Japan.|Chromosome Engineering Research Center, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503, Japan.
authors: Hiroyuki
authors: H
authors: Kugoh
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D014158:Transcription, Genetic; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C485621:KCNQ1OT1 long non-coding RNA, human; D009687:Nuclear Proteins; D027701:Organic Cation Transport Proteins; D024642:Potassium Channels, Voltage-Gated; D062085:RNA, Long Noncoding; C111653:SLC22A18 protein, human; C109277:TSSC3 protein; D051176:beta Catenin