title: A long non-coding RNA targets microRNA miR-34a to regulate colon cancer stem cell asymmetric division.
abstract: The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a, that is enriched in colon cancer stem cells (CCSCs) and initiates asymmetric division by directly targeting the microRNA miR-34a to cause its spatial imbalance. Lnc34a recruits Dnmt3a via PHB2 and HDAC1 to methylate and deacetylate the miR-34a promoter simultaneously, hence epigenetically silencing miR-34a expression independent of its upstream regulator, p53. Lnc34a levels affect CCSC self-renewal and colorectal cancer (CRC) growth in xenograft models. Lnc34a is upregulated in late-stage CRCs, contributing to epigenetic miR-34a silencing and CRC proliferation. The fact that lncRNA targets microRNA highlights the regulatory complexity of non-coding RNAs (ncRNAs), which occupy the bulk of the genome.
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Ithaca, United States.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Electrical and Computer Engineering, Cornell University, Ithaca, United States.|Department of Biomedical Engineering, Cornell University, Ithaca, United States.|Department of Biomedical Engineering, Duke University, Durham, United States.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Bu
authors.affiliation: School of Electrical and Computer Engineering, Cornell University, Ithaca, United States.|Department of Biomedical Engineering, Cornell University, Ithaca, United States.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Ai
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, United States.
authors.forename: Tara
authors.initials: T
authors.lastname: Srinivasan
authors.affiliation: Meyer Cancer Center, Weill Corenll Medical College, New York, United States.
authors.forename: Huanhuan Joyce
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, United States.
authors.forename: Kun
authors.initials: K
authors.lastname: Xiang
authors.affiliation: Deparments of Medicine, Genetic Medicine and Surgery, Weill Cornell Medical College, New York, United States.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Lipkin
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Ithaca, United States.|School of Electrical and Computer Engineering, Cornell University, Ithaca, United States.|Department of Biomedical Engineering, Cornell University, Ithaca, United States.|Department of Biomedical Engineering, Duke University, Durham, United States.
authors.forename: Xiling
authors.identifier: 0000-0002-4978-3531
authors.initials: X
authors.lastname: Shen
mesh_terms: D002455:Cell Division; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D020868:Gene Silencing; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D000091402:Prohibitins; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000378:metabolism*; D013234:Stem Cells / Q000502:physiology*
chemical_list: C000717967:DNMT3A protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C000717331:PHB2 protein, human; D000091402:Prohibitins; D062085:RNA, Long Noncoding; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1
keywords: asymmetric division; cancer biology; cancer stem cell; colon cancer; developmental biology; human; methylation; non-coding RNA; stem cells