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

Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States
Cancer Research (Impact Factor: 9.28). 04/2007; 67(6):2456-68. DOI: 10.1158/0008-5472.CAN-06-2698
Source: PubMed

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 microRNA 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.

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Available from: David Alan Jewell, Aug 11, 2015
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    • "Numerous studies showed that miR-203 has tumor suppressor functions in various cancer types (Gaur et al., 2007; Bueno et al., 2008; Feber et al., 2008) as its expression was abolished by chromosomal deletion or promoter CpG island hypermethylation in cancer cells (Bueno et al., 2008; Furuta et al., 2010). MiR-203 transcription was specifically repressed by the epithelial–mesenchymal translation (EMT) activator ZEB1, contributing to pancreatic and colorectal cancer cell invasive and metastatic behavior (Wellner et al., 2009). "
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    The International Journal of Biochemistry & Cell Biology 07/2014; 54. DOI:10.1016/j.biocel.2014.06.018
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    • "Partners of Dicer and the RISC complex, such as EIF2C1–4 (Argonaute- 1–4-like proteins), the DEAD box RNA helicase Gemin3–4, HSPCA (Hsp90) and PACT are also part of the miRNA machinery [22]. It has been observed that in cancer cells, the global levels of miRNAs are decreased [23] [24]. A relevant study showed that a general decrease in miRNAs caused by knockdown of Dicer and Drosha promoted tumorigenesis [25]. "
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    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 04/2014; 1845(2). DOI:10.1016/j.bbcan.2014.02.002
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    • "The treatment of cancer is rapidly evolving due to an improved understanding of the signaling pathways that are activated in tumors. Global profiling of DNA mutations, chromosomal copy number changes, DNA methylations and gene expression have greatly improved our appreciation of the heterogeneity of cancer [Nishizuka et al. (2003), Blower et al. (2007), Gaur et al. (2007), Shankavaram et al. (2007), Ehrich et al. (2008)]. However, the characterization of protein signaling networks has proven to be much more challenging. "
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