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Publication : Strand-specific in vivo screen of cancer-associated miRNAs unveils a role for miR-21(∗) in SCC progression.

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.
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