Characterization of MicroRNA Expression Levels and Their Biological Correlates in Human Cancer Cell Lines

Abstract

MicroRNAs are small noncoding RNAs that function by regulating target gene expression posttranscriptionally. They play a critical role in developmental and physiologic processes and are implicated in the pathogenesis of several human diseases including cancer. We examined the expression profiles of 241 human microRNAs in normal tissues and the NCI-60 panel of human tumor-derived cell lines. To quantify micro-RNA expression, we employed a highly sensitive technique that uses stem-loop primers for reverse transcription followed by real-time PCR. Most microRNAs were expressed at lower levels in tumor-derived cell lines compared with the corresponding normal tissue. Agglomerative hierarchical clustering analysis of microRNA expression revealed four groups among the NCI-60 cell lines consisting of hematologic, colon, central nervous system, and melanoma tumor-derived cell lines clustered in a manner that reflected their tissue of origin. We identified specific subsets of microRNAs that provide candidate molecular signatures characteristic of the tumor-derived cell lines belonging to these four clusters. We also identified specific microRNA expression patterns that correlated with the proliferation indices of the NCI-60 cell lines, and we developed evidence for the identification of specific microRNAs as candidate oncogenes and tumor suppressor genes in different tumor types. Our results provide evidence that microRNA expression patterns may mark specific biological characteristics of tumors and/or mediate biological activities important for the pathobiology of malignant tumors. These findings call attention to the potential of microRNAs to provide etiologic insights as well as to serve as both diagnostic markers and therapeutic targets for many different tumor types. [Cancer Res 2007;67(6):2456-68]

miR-449a targets HDAC-1 and induces growth arrest in prostate cancer

“…Microarray studies have characterized the modulation of miRNA expression in prostate cancer as compared with normal prostate tissue and identified a number of miRNAs that are up-or downregulated in prostate tumors (Jiang et al, 2005;Mattie et al, 2006;Volinia et al, 2006;Gaur et al, 2007;Porkka et al, 2007;Ozen et al, 2008). In all of these studies, miRNA expression profiles were based on the current databases of miRNAs known at the time (Volinia et al, 2006).…”

“…Dysregulation of miRNA expression has been identified in a number of cancers (Pan et al, 2001;Lu et al, 2005;Volinia et al, 2006;Blenkiron et al, 2007;Chen and Stallings, 2007;Fulci et al, 2007;Gaur et al, 2007;Kummar et al, 2007;Meng et al, 2007;Porkka et al, 2007;Wedel et al, 2008) and an accumulating data indicate that some miRNAs can function as tumor suppressors or oncogenes and are important in cancer development. Deletion or loss of function of a tumor-suppressing miRNA results in overexpression of target oncogenes.…”

MiR-135a functions as a selective killer of malignant glioma

“…Independent research groups have reported significant miRNA alteration in glioma by profiling (Gaur et al, 2007;Malzkorn et al, 2010). Among these aberrant miRNAs in malignant glioma, miR-124 and miR-128 are better characterized.…”

microRNA-10b is a prognostic biomarker for melanoma

“…3 In melanoma, miRNAs can be readily analyzed from formalin-fixed paraffin-embedded tissue, 4 show high frequency genetic alterations, 5 and exhibit a melanoma-specific signature. 6 In addition, miRNAs have shown prognostic value in melanoma. [7][8][9][10][11] A panel of six miRNAs was identified as a post-recurrence survival signature, 9 and miRNA and mRNA networks were associated with the outcome, 11 while a 4-miRNA signature was associated with brain metastasis.…”