miR-21 Gene Expression Triggered by AP-1 Is Sustained through a Double-Negative Feedback Mechanism

摘要: miR-21 has been reported to be highly expressed in various cancers and inducible a human promyelocytic cell line, HL-60, after phorbol 12-myristate 13-acetate (PMA) treatment. To examine molecular mechanisms involved expression, we analyzed the structure of gene by determining its promoter primary transcripts. We show that activation protein 1 (AP-1) activates transcription conjugation with SWI/SNF complex, PMA stimulation, through conserved AP-1 PU.1 binding sites identified here. The previous findings enhanced expression several may therefore reflect elevated activity these carcinomas. A single precursor RNA containing was transcribed just downstream from TATA box this promoter, which is located an intron coding gene, TMEM49. More important, overlapping completely PMA-independent all transcripts are polyadenylated before reaching hairpin embedding region, indicating miRNAs could have their own even if overlapped other genes. By available algorithms predict miRNA target using conservation sequence complementary seed sequence, next predicted confirmed NFIB mRNA miR-21. usually binds HL-60 cells as negative regulator swept off during PMA-induced macrophage differentiation HL-60. translational repression accelerates clearance parallel simultaneous miR-21-independent transcriptional stimulation. Since exogenous moderately induced endogenous miR-21, evolutionarily double-negative feedback regulation would operating mechanism sustain expression.