title: CUDR promotes liver cancer stem cell growth through upregulating TERT and C-Myc.
abstract: Cancer up-regulated drug resistant (CUDR) is a novel non-coding RNA gene. Herein, we demonstrate excessive CUDR cooperates with excessive CyclinD1 or PTEN depletion to accelerate liver cancer stem cells growth and liver stem cell malignant transformation in vitro and in vivo. Mechanistically, we reveal the decrease of PTEN in cells may lead to increase binding capacity of CUDR to CyclinD1. Therefore, CUDR-CyclinD1 complex loads onto the long noncoding RNA H19 promoter region that may lead to reduce the DNA methylation on H19 promoter region and then to enhance the H19 expression. Strikingly, the overexpression of H19 increases the binding of TERT to TERC and reduces the interplay between TERT with TERRA, thus enhancing the cell telomerase activity and extending the telomere length. On the other hand, insulator CTCF recruits the CUDR-CyclinD1 complx to form the composite CUDR-CyclinD1-insulator CTCF complex which occupancied on the C-myc gene promoter region, increasing the outcome of oncogene C-myc. Ultimately, excessive TERT and C-myc lead to liver cancer stem cell and hepatocyte-like stem cell malignant proliferation. To understand the novel functions of long noncoding RNA CUDR will help in the development of new liver cancer therapeutic and diagnostic approaches.
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Pu
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Qidi
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Wu
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: An
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gui
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C515159:UCA1 RNA, human; C509186:TERT protein, human; D019098:Telomerase
keywords: CUDR; PTEN; liver cancer stem cell