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.

SUBMITTER: Ge Y 

PROVIDER: S-EPMC5333577 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature