Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest.
miRNAs regulate gene expression by inhibiting translation or by targeting messenger RNA (mRNA) for degradation in a post-transcriptional fashion. In the present study, we show that ectopic expression of miR-34a reduces both mRNA and protein levels of cyclin D1 (CCND1) and cyclin-dependent kinase 6 (CDK6). We also demonstrate that miR-34a targets the 3'-untranslated mRNA region of CCND1 as well as CDK6, which in turn interferes with phosphorylation of retinoblastoma. In addition, we show that overexpression of miR-34a induces a significant G1 cell-cycle arrest in the A549 cell line. Taken together, our data suggest that the effects of miR-34a on G1 cell cycle arrest are through the down-regulation of CCND1 and CDK6, which is associated with other targets of miR-34a either additively or synergistically.
Sun
Fang
F
Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.
Fu
Hanjiang
H
Liu
Qin
Q
Tie
Yi
Y
Zhu
Jie
J
Xing
Ruiyun
R
Sun
Zhixian
Z
Zheng
Xiaofei
X
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D056741:Cyclin D; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics*; D016213:Cyclins / Q000235:genetics*; D015536:Down-Regulation; D016193:G1 Phase / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D056741:Cyclin D; D016213:Cyclins; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6