First Author | Ge Y | Year | 2016 |
Journal | Nat Cell Biol | Volume | 18 |
Issue | 1 | Pages | 111-21 |
PubMed ID | 26619149 | Mgi Jnum | J:230732 |
Mgi Id | MGI:5763689 | Doi | 10.1038/ncb3275 |
Citation | Ge Y, et al. (2016) Strand-specific in vivo screen of cancer-associated miRNAs unveils a role for miR-21( *) in SCC progression. Nat Cell Biol 18(1):111-21 |
abstractText | MicroRNAs play diverse roles in both normal and malignant stem cells. Focusing on miRs and/or miR( *)s abundant in squamous cell carcinoma (SCC) stem cells, we engineer an efficient, strand-specific expression library, and apply functional genomics screening in mice to identify which of 169 cancer-associated miRs are key drivers in malignant progression. Not previously linked functionally to cancer, miR-21( *) was the second top hit, surfacing in >12% of tumours. miR-21( *) also correlates with poor prognosis in human SCCs and enhances tumour progression in xenografts. On deleting the miR-21 gene and rescuing each strand separately, we document the dual, but independent, oncogenicity of miR-21 and miR-21( *). A cohort of predicted miR-21( *) targets inversely correlate with miR-21( *) in SCCs. Of particular interest is Phactr4, which we show is a miR-21( *) target in SCCs, acting through the Rb/E2F cell cycle axis. Through in vivo physiological miR screens, our findings add an interesting twist to an increasingly important oncomiR locus. |