title: Long Non-Coding RNA CCAT1 Acts as a Competing Endogenous RNA to Regulate Cell Growth and Differentiation in Acute Myeloid Leukemia.
abstract: Long non-coding RNAs (lncRNAs) are involved in multiple cellular events, as well as in tumorigenesis. Colon cancer-associated transcript-1 (CCAT1) gene encodes an lncRNA whose over-activation was observed in an expanding list of primary human solid tumors and tumor cell lines, however its biological roles in acute myeloid leukaemia (AML) has not been reported yet at present. In this study, the aberrant upregulation of CCAT1 was detected in French-American-British M4 and M5 subtypes of adult AML patients. By gain- and loss-of-function analysis, we determined that CCAT1 repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. Accordingly, a significant decrease in miR-155 level was detected in AML patients. Re-introduction of miR-155 into HL-60 cells restored monocytic maturation and repressed cell proliferation. Furthermore, CCAT1 could up-regulated c-Myc via its competing endogenous RNA (ceRNA) activity on miR-155. In conclusion, these results revealed new mechanism of lncRNA CCAT1 in AML development, and suggested that the manipulation of CCAT1 expression could serve as a potential strategy in AML therapy.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010059, China.
authors.forename: Lianxiang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Emergency, Inner Mongolia People's Hospital, Hohhot 010017, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010059, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Anatomy, Basic Medical College, The Inner Mongolia Medical University, Hohhot 010059, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Anatomy, Basic Medical College, The Inner Mongolia Medical University, Hohhot 010059, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C579842:CCAT1 long noncoding RNA, human; C524942:MIRN155 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding
keywords: AML; CCAT1; lncRNA; miR-155