title: microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells.
abstract: microRNAs (miRNA) are small noncoding RNAs that participate in diverse biological processes by suppressing target gene expression. Altered expression of miR-21 has been reported in cancer. To gain insights into its potential role in tumorigenesis, we generated miR-21 knockout colon cancer cells through gene targeting. Unbiased microarray analysis combined with bioinformatics identified cell cycle regulator Cdc25A as a miR-21 target. miR-21 suppressed Cdc25A expression through a defined sequence in its 3'-untranslated region. We found that miR-21 is induced by serum starvation and DNA damage, negatively regulates G(1)-S transition, and participates in DNA damage-induced G(2)-M checkpoint through down-regulation of Cdc25A. In contrast, miR-21 deficiency did not affect apoptosis induced by a variety of commonly used anticancer agents or cell proliferation under normal cell culture conditions. Furthermore, miR-21 was found to be underexpressed in a subset of Cdc25A-overexpressing colon cancers. Our data show a role of miR-21 in modulating cell cycle progression following stress, providing a novel mechanism of Cdc25A regulation and a potential explanation of miR-21 in tumorigenesis.
authors.affiliation: Departments of Pathology and Pharmacology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Fangdong
authors.initials: F
authors.lastname: Zou
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Austin
authors.initials: A
authors.lastname: Dulak
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tomko
authors.forename: John S
authors.initials: JS
authors.lastname: Lazo
authors.forename: Zhenghe
authors.initials: Z
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
mesh_terms: D017209:Apoptosis; D001973:Bromodeoxyuridine; D002453:Cell Cycle; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004249:DNA Damage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology*; D008940:Mitotic Index; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020687:cdc25 Phosphatases
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D008156:Luciferases; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases; D001973:Bromodeoxyuridine