MicroRNA-1285 inhibits the expression of p53 by directly targeting its 3' untranslated region.
The well-known tumor suppressor p53 plays critical roles in the modulation of multiple cellular processes. The regulation of p53 is complicated and remains elusive. In this study, we used a high-throughput luciferase reporter screen to demonstrate that p53 can be regulated by microRNA-1285 (miR-1285). Notably, miR-612, which has the same seed sequence as miR-1285, cannot bind to the 3' untranslated region (3' UTR) of p53. Mutational analyses confirmed that the 3' UTR of p53 mRNA contains two miR-1285 target sites, which are nearly perfectly complementary to the mature miR-1285 sequence. Ectopic expression of miR-1285 inhibits expression of p53 mRNA and protein. In contrast, silencing of miR-1285 increases p53 expression. Furthermore, miR-1285 inhibits the transcription of p21, a master gene downstream of p53. In conclusion, our findings provide the first evidence that miR-1285 directly regulates the expression of p53 by directly targeting its 3' UTR.
Tian
Shu
S
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China.
Huang
Shenglin
S
Wu
Shunquan
S
Guo
Weijian
W
Li
Jin
J
He
Xianghuo
X
D020413:3' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics*
D020413:3' Untranslated Regions; D050759:Cyclin-Dependent Kinase Inhibitor p21; C572554:MIRN1285 microRNA, human; C582274:MIRN612 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D008156:Luciferases