A microRNA expression signature of human solid tumors defines cancer gene targets

Volinia, Stefano; Calin, George A.; Liu, Chang Gong; Ambs, Stefan; Cimmino, Amelia; Petrocca, Fabio; Visone, Rosa; Iorio, Marilena V.; Roldo, Claudia; Ferracin, Manuela; Prueitt, Robyn L.; Yanaihara, Nozumu; Lanza, Giovanni; Scarpa, Aldo; Vecchione, Andrea; Negrini, Massimo; Harris, Curtis C.; Croce, Carlo M.

doi:10.1073/pnas.0510565103

Cited by 5,172 publications

(4,646 citation statements)

References 28 publications

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“…The function of miRNAs may be deregulated in cancer in several manners, including miRNA gene mutation, deletion or promoter hypermethylation, but also as a consequence of mutations in their target sequences (Esquela‐Kerscher and Slack, 2006; Nana‐Sinkam and Croce, 2011; Palmero et al., 2011). Although attenuated expression of the miRNA transcriptome is frequently observed (Kumar et al., 2007; Lu et al., 2005), various miRNAs are overexpressed in specific tumors compared to their healthy tissue of origin (Ma et al., 2010a,b; Volinia et al., 2006), and thus are termed “oncomiRs”. Furthermore, the predicted targets for several cancer‐associated miRNAs include protein‐coding tumor suppressors and oncogenes, supporting a role for miRNAs in cancer pathogenesis (Esquela‐Kerscher and Slack, 2006; Nana‐Sinkam and Croce, 2011; Palmero et al., 2011).…”

Section: Addressing Tumor Heterogeneity and Complexitymentioning

confidence: 99%

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

2012

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It is a time of great promise and expectation for the applications of knowledge about mechanisms of cancer toward more effective and enduring therapies for human disease. Conceptualizations such as the hallmarks of cancer are providing an organizing principle with which to distill and rationalize the abject complexities of cancer phenotypes and genotypes across the spectrum of the human disease. A countervailing reality, however, involves the variable and often transitory responses to most mechanism‐based targeted therapies, returning full circle to the complexity, arguing that the unique biology and genetics of a patient's tumor will in the future necessarily need to be incorporated into the decisions about optimal treatment strategies, the frontier of personalized cancer medicine. This perspective highlights considerations, metrics, and methods that may prove instrumental in charting the landscape of evaluating individual tumors so to better inform diagnosis, prognosis, and therapy. Integral to the consideration is remarkable heterogeneity and variability, evidently embedded in cancer cells, but likely also in the cell types composing the supportive and interactive stroma of the tumor microenvironment (e.g., leukocytes and fibroblasts), whose diversity in form, regulation, function, and abundance may prove to rival that of the cancer cells themselves. By comprehensively interrogating both parenchyma and stroma of patients' cancers with a suite of parametric tools, the promise of mechanism‐based therapy may truly be realized.

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Section: Addressing Tumor Heterogeneity and Complexitymentioning

confidence: 99%

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

2012

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“…This screening showed that miR‐21, miR‐191, and miR‐17‐5p are significantly upregulated in all of the tumor types and that miR‐29b‐2, miR‐223, miR‐128b, miR‐199a‐1, miR‐24‐1, miR‐24‐2, miR‐146, miR‐155, miR‐181b‐1, miR‐20a, miR‐107, miR‐32, miR‐92, miR‐214, miR‐30c, miR‐25, miR‐221, and miR‐106a were overexpressed in three or more types of solid cancers (Volinia et al ., 2006). After identifying the presence of miRNAs in solid tumors, circulating miRNA signatures have been widely described in many cancer types (Chen et al ., 2008; Lawrie et al ., 2008; Mitchell et al ., 2008).…”

Section: Circulating Mirnas As Biomarkersmentioning

confidence: 99%

Cell‐to‐cell communication: microRNAs as hormones

2017

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Mammalian cells can release different types of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies. Accumulating evidence suggests that EVs play a role in cell‐to‐cell communication within the tumor microenvironment. EVs’ components, such as proteins, noncoding RNAs [microRNAs (miRNAs), and long noncoding RNAs (lncRNAs)], messenger RNAs (mRNAs), DNA, and lipids, can mediate paracrine signaling in the tumor microenvironment. Recently, miRNAs encapsulated in secreted EVs have been identified in the extracellular space. Mature miRNAs that participate in intercellular communication are released from most cells, often within EVs, and disseminate through the extracellular fluid to reach remote target cells, including tumor cells, whose phenotypes they can influence by regulating mRNA and protein expression either as tumor suppressors or as oncogenes, depending on their targets. In this review, we discuss the roles of miRNAs in intercellular communication, the biological function of extracellular miRNAs, and their potential applications for diagnosis and therapeutics. We will give examples of miRNAs that behave as hormones.

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“…35 Interestingly, the majority of HRMs are also overexpressed in at least some types of tumor types, suggesting that hypoxia represents a contributing element for microRNA alterations in cancer.…”

Section: Towards Future Applications In Clinical Oncologymentioning

confidence: 99%

A microRNA component of the hypoxic response

et al. 2008

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microRNAs participate in a wide variety of physiological and pathological cellular processes. Recent studies have established a link between a specific group of microRNAs and hypoxia, a key feature of the neoplastic microenvironment. A significant proportion of the hypoxia-regulated microRNAs (HRMs) are also overexpressed in human cancers, suggesting a role in tumorigenesis. Preliminary evidence suggests that they could affect important processes such as apoptosis, proliferation and angiogenesis. Several HRMs exhibit induction in response to HIF activation, thus extending its repertoire of targets beyond translated genes. In the present review, we discuss the emerging roles of HRMs in oxygen deprivation in cancer context.

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A microRNA expression signature of human solid tumors defines cancer gene targets

Cited by 5,172 publications

References 28 publications

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

Cell‐to‐cell communication: microRNAs as hormones

A microRNA component of the hypoxic response

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