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: 9.33). 04/2007; 67(6):2456-68. DOI: 10.1158/0008-5472.CAN-06-2698
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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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    • "Recent studies have indicated that expression profiles of miRNAs are associated with patients' survival and are able to function as prognostic and predictive indicators in glioma, based on public database entries [7] [8] [9] [10] [11] or independent tissue cohorts [12] [13] [14] [15]. Most of these identified miRNAs have also been proved to be involved in the tumorigenesis and function as oncogenes or tumor suppressors in human gliomas, such as miR-21 [16] [17], miR-155 [18] [19] [20], miR- 196 [21] [22], miR-221/222 [23] and miR-326 [24] [25]. Thus, the identification of the miRNA expression signature for malignant gliomas, in particular glioblastoma, is of great significance not only for predicting clinical outcomes, but also for understanding the molecular mechanisms of tumorigenesis and developing novel therapeutics of these malignancies. "
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    ABSTRACT: Identification of microRNAs (miRNAs) could be beneficial for the diagnosis and prognosis of glioma. Therefore, we attempted to identify and develop specific miRNAs as prognostic and predictive markers for glioma patients. We compared the expression profiles of 365 miRNAs between 4 glioblastomas (GBMs, WHO grade IV) and 4 anaplastic astrocytomas (AAs, WHO grade III) using miRNA qPCR Array. MiR-196a (P = 0.004, fold change = 289.86) and miR-367 (P = 0.044, fold change = 0.03) were identified as the most up-regulated and down-regulated miRNAs in GBMs compared with AAs, respectively. We subsequently examined miR-196a and miR-367 expression levels in an independent series of 63 gliomas including 50 GBMs and 13 AAs, as well as 10 non-neoplastic brain tissues, and statistically analyzed the associations between miRNA expression and clinicopathological characteristics and survivals of these glioma patients. MiR-196a and miR-367 showed significant increased and decreased expression in high-grade gliomas relative to non-neoplastic brains, as well as in GBMs versus AAs, respectively. Additionally, high-miR-196a and low-miR-367 expression, alone or in combination, statistically correlated with aggressive clinicopathological features of gliomas. Furthermore, overall survivals of glioma patients with high-miR-196a, low-miR-367 and high-miR-196a/low-miR-367 expression tended to be shorter than the corresponding control groups (all P ≤ 0.001). Moreover, multivariate analysis indicated high-miR-196a/low-miR-367 as an independent prognostic indicator for glioma patients (P = 0.005, risk ratio = 1.8). Our results suggested that both high-miR-196a and low-miR-367 expression may be associated with aggressive progression and unfavorable clinical outcome in glioma patients. And combination of high-miR-196a and low-miR-367 expression may be a novel biomarker in identifying a poor prognosis group of high-grade glioma.
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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 · 4.05 Impact Factor
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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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    ABSTRACT: Metastasis is a phenomenon of crucial importance in defining prognosis in patients with cancer and is often responsible for cancer-related mortality. It is known that several steps are necessary for clonal cells to disseminate from their primary tumor site and colonize distant tissues, thus originating metastatic lesions. Therefore, investigating the molecular actors regulating this process may provide helpful insights in the development of efficient therapeutic responses. Recent evidences have indicated the role of microRNAs (miRNAs) in modulating the metastatic process in solid tumors. miRNAs are small regulatory non-coding RNAs that bind specific target mRNAs, leading to translational repression. miRNAs are known to act as negative regulators of gene expression and are involved in the regulation of biological processes, including cell growth, differentiation and apoptosis, both in physiological conditions and during diseases, such as tumors. In the specific field of tumorigenesis, miRNAs play an important role in mediating oncogenesis and favoring tumor progression, as a result of their ability to modulate epithelial-to-mesenchymal transition (EMT) and other series of events facilitating the formation of metastasis. The role of miRNAs in cancer development has been widely studied and has helped elucidate events such as the change in expression of oncogenes, tumor-suppressors and cancer-related proteins. This review focuses on the mechanisms underlying the role of miRNAs as part of the metastatic process.
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