Lung Cancer

HMGA2[Coding-mRNA]

let-7a[miRNA]

TGFBR3[mRNA]

368T1 And 482N1 Cells

Mus musculus (mouse)

Nature 2014 Jan 9 505, 212-7 doi:10.1038/nature12785 PMID:24305048

Hmga2 functions as a competing endogenous RNA to promote lung cancer progression.

Western blot;qRT-PCR;luciferase reporter assays

Here we show that Hmga2 promotes lung cancer progression in mouse and human cells by operating as a competing endogenous RNA (ceRNA) for the let-7 microRNA (miRNA) family. Hmga2 can promote the transformation of lung cancercells independent of protein-coding function but dependent upon the presence of let-7 sites; this occurs without changes in the levels of let-7 isoforms, suggesting that Hmga2 affects let-7 activity by altering miRNA targeting. These effects are also observed in vivo, where Hmga2 ceRNA activity driveslung cancer growth, invasion and dissemination. Finally, analysis of NSCLC-patient gene-expression data reveals that HMGA2 and TGFBR3 are coordinately regulated in NSCLC-patient material, a vital corollary to ceRNA function. Taken together, these results suggest that Hmga2 promotes lung carcinogenesis both as a protein-coding gene and as a non-coding RNA; such dual-function regulation of gene-expression networks reflects a novel means by which oncogenes promote disease progression.