Suppression of p21 by c-Myc through members of miR-17 family at the post-transcriptional level

Abstract

The miR-17 family, composed of miR-17-5p, miR-20a/b, miR-106a/b and miR-93, has been demonstrated to take part in critical pathways that regulate cellular life and death decisions during normal development and in malignancy. Previous studies have shown that the expression of miR-17 family members has close relationship with the expression of c-Myc. Another study has reported p21 is a direct target of miR-17 family and their silencing of p21 contributes to tumor cell proliferation in part. Since c-Myc is a potent transcriptional repressor of p21, these findings suggest that c-Myc may negatively modulate p21 expression through an additional pathway except transcriptional suppression. In the study presented here, we compared p21 mRNA in the nucleus and cytoplasm of c-Myc stable transfectants with its control, which indicated further repression of p21 by c-Myc at the post-transcriptional level. Stem-loop and conventional real-time PCR showed elevated expression of some members in miR-17 family and their primary transcripts when c-Myc was stably overexpressed. To further investigate the relationship of c-Myc, miR-17 family and p21, we antagonized the expression of each miR-17 family member by transfection of their antisense oligonucleotides respectively in transfectants constitutively overexpressing c-Myc or not, and found that the restoration of p21 expression by treatment above was much stronger in the presence of c-Myc. These results suggest c-Myc could further repress p21 expression at the posttranscriptional level through some, but not all, members of miR-17 family.