title: MicroRNA-188 suppresses G1/S transition by targeting multiple cyclin/CDK complexes.
abstract: BACKGROUND
  Accelerated cell cycle progression is the common feature of most cancers. MiRNAs can act as oncogenes or tumor suppressors by directly modulating cell cycle machinery. It has been shown that miR-188 is upregulated in UVB-irradiated mouse skin and human nasopharyngeal carcinoma CNE cells under hypoxic stress. However, little is known about the function of miR-188 in cell proliferation and growth control.
  
  
  RESULTS
  Overexpression of miR-188 inhibits cell proliferation, tumor colony formation and G1/S cell cycle transition in human nasopharyngeal carcinoma CNE cells. Using bioinformatics approach, we identify a series of genes regulating G1/S transition as putative miR-188 targets. MiR-188 inhibits both mRNA and protein expression of CCND1, CCND3, CCNE1, CCNA2, CDK4 and CDK2, suppresses Rb phosphorylation and downregulates E2F transcriptional activity. The expression level of miR-188 also inversely correlates with the expression of miR-188 targets in human nasopharyngeal carcinoma (NPC) tissues. Moreover, studies in xenograft mouse model reveal that miR-188 is capable of inhibiting tumor initiation and progression by suppressing target genes expression and Rb phosphorylation.
  
  
  CONCLUSIONS
  This study demonstrates that miR-188 exerts anticancer effects, via downregulation of multiple G1/S related cyclin/CDKs and Rb/E2F signaling pathway.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, 100084, PR China. wyh0794@gmail.com.|Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. wyh0794@gmail.com.
authors.forename: Jiangbin
authors.initials: J
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, 100084, PR China. lvtsing@gmail.com.|Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. lvtsing@gmail.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. jie.he2004@gmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, 100084, PR China. 380847315@qq.com.|Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. 380847315@qq.com.
authors.forename: Haoxiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: ENT Department, Peking University Shenzhen Hospital, Shenzhen, 518055, PR China. xueshuang_mei@163.com.
authors.forename: Xueshuang
authors.initials: X
authors.lastname: Mei
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, 100084, PR China. cui.kai1107@gmail.com.|Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. cui.kai1107@gmail.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Cui
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, 100084, PR China. huangnunu2781781@126.com.|Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. huangnunu2781781@126.com.
authors.forename: Nunu
authors.initials: N
authors.lastname: Huang
authors.affiliation: Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. xiewd@sz.tsinghua.edu.cn.
authors.forename: Weidong
authors.initials: W
authors.lastname: Xie
authors.affiliation: Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. xu.naihan@sz.tsinghua.edu.cn.
authors.forename: Naihan
authors.initials: N
authors.lastname: Xu
authors.affiliation: Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. zhangyo@sz.tsinghua.edu.cn.
authors.forename: Yaou
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism; D006801:Humans; D007399:Interphase / Q000502:physiology*; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D016213:Cyclins; D050684:E2F Transcription Factors; C584093:MIRN188 microRNA, human; D035683:MicroRNAs; D016160:Retinoblastoma Protein; D018844:Cyclin-Dependent Kinases