Details

Autor(en) / Beteiligte

• Kumar, Madhu S
• Erkeland, Stefan J
• Pester, Ryan E
• Chen, Cindy Y
• Ebert, Margaret S
• Sharp, Phillip A
• Jacks, Tyler

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2008-03, Vol.105 (10), p.3903-3908

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2008

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Many microRNAs (miRNAs) target mRNAs involved in processes aberrant in tumorigenesis, such as proliferation, survival, and differentiation. In particular, the let-7 miRNA family has been proposed to function in tumor suppression, because reduced expression of let-7 family members is common in non-small cell lung cancer (NSCLC). Here, we show that let-7 functionally inhibits non-small cell tumor development. Ectopic expression of let-7g in K-RasG¹²D-expressing murine lung cancer cells induced both cell cycle arrest and cell death. In tumor xenografts, 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-RasG¹²D 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.