Gene expression in both healthy and cancerous tissues is controlled by a wide array of regulatory molecules including a group of small RNA molecules known as microRNAs. New research, performed by Ethan Dmitrovsky and colleagues, at Dartmouth Medical School, Hanover, now provides evidence that the microRNA miR-31 promotes lung cancer by repressing the expression of a number of tumor suppressor genes (i.e., genes that generate proteins that suppress the development of cancer).
The initial series of experiments conducted in the study indicated that miR-136, miR-376a, and miR-31 were all overexpressed in mouse and human malignant lung tissue compared with paired normal tissue. Importantly, knockdown of miR-31 expression repressed the in vitro growth of mouse and human lung cancer cell lines and reduced the in vivo tumorigenicity of mouse lung cancer cell lines.
Further analysis provided a potential mechanism by which modulation of miR-31 expression levels could affect lung cancer cell growth: miR-31 repressed expression of the tumor-suppressor genes LATS2 and PPP2R2A. As miR-31 and these target genes were inversely expressed in human lung cancers, the authors conclude that their data has clinical relevance and that miR-31 promotes lung cancer by repressing expression of specific tumor suppressors.
The research appears in the Journal of Clinical Investigation.
- Xi Liu, Lorenzo F. Sempere, Haoxu Ouyang, Vincent A. Memoli, Angeline S. Andrew, Yue Luo, Eugene Demidenko, Murray Korc, Wei Shi, Meir Preis, Konstantin H. Dragnev, Hua Li, James Direnzo, Mads Bak, Sarah J. Freemantle, Sakari Kauppinen, and Ethan Dmitrovsky. MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI39566
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