Expression levels of microRNAs (miRNAs) are globally reduced in cancer compared 
with matched normal tissues, and miRNA function has recently been implicated in 
tumorigenesis. To test whether epigenetic silencing contributes to miRNA 
suppression in tumors, lung cancer cells were treated with inhibitors of DNA 
methylation or histone deacetylation. No significant alteration in miRNA 
expression was detected using microarray profiling. To search for 
tumor-associated mutations that could affect processing and expression of mature 
miRNAs, a panel of 91 cancer-derived cell lines was analyzed for sequence 
variations in 15 miRNAs implicated in tumorigenesis by virtue of their known 
target transcripts (let-7 family targeting oncogenic Ras) or their localization 
to sites of frequent chromosomal instability (miR-143, miR-145, miR-26a-1, and 
miR-21). No mutations were detected within any of the short mature miRNA 
sequences. In addition to previously reported polymorphisms, 1 sequence variant 
in a precursor miRNA and 15 variants in primary miRNA (pri-miRNA) transcripts 
were identified. Despite pri-miRNAs having dramatic changes in the predicted 
secondary folding structure flanking putative cleavage sites, processing and 
miRNA maturation were not affected in vivo. Thus, genetic variants in miRNA 
precursors are common in cancer cells but are unlikely to have physiologic 
significance.