Non-Small Cell Lung Cancer

LKR13-Tet-On-KRAB-TE-let-7g[Artifically engineered RNA]

let-7c[miRNA]

HMGA2[mRNA]

Hek293, A549, Calu-1, And H1650

Mus musculus (mouse)

Proc Natl Acad Sci U S A 2008 Mar 11 105, 3903-8 doi:10.1073/pnas.0712321105 PMID:18308936

Suppression of non-small cell lung tumor development by the let-7 microRNA family

Luciferase reporter assay

Here, we show that let-7 functionally inhibits non-small cell tumor development. Ectopic expression of let-7g in K-Ras(G12D)-expressing murine lung cancer cells induced both cell cycle arrest and cell death. In tumorxenografts, we observed significant growth reduction of both murine and human non-small cell lung tumors when overexpression of let-7g was induced from lentiviral vectors. In let-7g expressing tumors, reductions in Ras family and HMGA2 protein levels were detected. Importantly, let-7g-mediated tumor suppression was more potent in lung cancer cell lines harboring oncogenic K-Ras mutations than in lines with other mutations. Ectopic expression of K-Ras(G12D) largely rescued let-7g mediated tumor suppression, whereas ectopic expression of HMGA2 was less effective. Finally, in an autochthonous model of NSCLC in the mouse, let-7g expression substantially reduced lung tumor burden.