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

Nat Cell Biol. 2016 Jan;18(1):111-21. doi: 10.1038/ncb3275. Epub 2015 Nov 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics*
  • Mice
  • MicroRNAs / genetics*


  • MIRN21 microRNA, mouse
  • MicroRNAs