title: Strand-specific in vivo screen of cancer-associated miRNAs unveils a role for miR-21(∗) in SCC progression.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, New York 10065, USA.
authors.forename: Yejing
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, New York 10065, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, New York 10065, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Nikolova
authors.affiliation: Department of Genetics and Genomic Sciences, Mt. Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Reva
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, New York 10065, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*
chemical_list: C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs