You are here

Nat Genet DOI:10.1038/ng2003

Impaired microRNA processing enhances cellular transformation and tumorigenesis.

Publication TypeJournal Article
Year of Publication2007
AuthorsKumar, MS, Lu, J, Mercer, KL, Golub, TR, Jacks, T
JournalNat Genet
Date Published2007 May
KeywordsAnimals, Bromodeoxyuridine, Carcinogenicity Tests, Cell Line, Tumor, Cell Transformation, Neoplastic, Flow Cytometry, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Humans, Immunoblotting, Luciferases, Mice, MicroRNAs, Neoplasms, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease III

MicroRNAs (miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate the expression of target mRNA transcripts. Many of these target mRNA transcripts are involved in proliferation, differentiation and apoptosis, processes commonly altered during tumorigenesis. Recent work has shown a global decrease of mature miRNA expression in human cancers. However, it is unclear whether this global repression of miRNAs reflects the undifferentiated state of tumors or causally contributes to the transformed phenotype. Here we show that global repression of miRNA maturation promotes cellular transformation and tumorigenesis. Cancer cells expressing short hairpin RNAs (shRNAs) targeting three different components of the miRNA processing machinery showed a substantial decrease in steady-state miRNA levels and a more pronounced transformed phenotype. In animals, miRNA processing-impaired cells formed tumors with accelerated kinetics. These tumors were more invasive than control tumors, suggesting that global miRNA loss enhances tumorigenesis. Furthermore, conditional deletion of Dicer1 enhanced tumor development in a K-Ras-induced mouse model of lung cancer. Overall, these studies indicate that abrogation of global miRNA processing promotes tumorigenesis.


Alternate JournalNat. Genet.
PubMed ID17401365
Grant List2-P01-CA42063-21 / CA / NCI NIH HHS / United States
P30-CA14051 / CA / NCI NIH HHS / United States