title: Oncogenic micro-RNAs and Renal Cell Carcinoma.
abstract: Tumor formation is a complex process that occurs in different steps and involves many cell types, including tumor cells, endothelial cells, and inflammatory cells, which interact to promote growth of the tumor mass and metastasization. Epigenetic alterations occurring in transformed cells result in de-regulation of miRNA expression (a class of small non-coding RNA that regulates multiple functions), which contributes to tumorigenesis. The specific miRNAs, which have an aberrant expression in tumors, are defined as oncomiRNAs, and may be either over- or under-expressed, but down-regulation is most commonly observed. Renal cell carcinoma (RCC) is a frequent form of urologic tumor, associated with an alteration of multiple signaling pathways. Many molecules involved in the progression of RCCs, such as HIF, VEGF, or mammalian target of rapamycin, are possible targets of de-regulated miRNAs. Within tumor mass, the cancer stem cell (CSC) population is a fundamental component that promotes tumor growth. The CSC hypothesis postulates that CSCs have the unique ability to self-renew and to maintain tumor growth and metastasis. CSCs present in RCC were shown to express the mesenchymal stem cell marker CD105 and to exhibit self-renewal and clonogenic properties, as well as the ability to generate serially transplantable tumors. The phenotype of CSC has been related to the potential to undergo the epithelial-mesenchymal transition, which has been linked to the expression pattern of tumorigenic miRNAs or down-regulation of anti-tumor miRNAs. In addition, the pattern of circulating miRNAs may allow discrimination between healthy and tumor patients. Therefore, a miRNA signature may be used as a tumor biomarker for cancer diagnosis, as well as to classify the risk of relapse and metastasis, and for a guide for therapy.
authors.affiliation: Department of Medical Sciences, University of Torino , Torino , Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Grange
authors.affiliation: Translational Center for Regenerative Medicine, University of Torino , Torino , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Collino
authors.affiliation: Department of Medical Sciences, University of Torino , Torino , Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Tapparo
authors.affiliation: Department of Medical Sciences, University of Torino , Torino , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
keywords: EMT transition; RCC biomarkers; cancer stem cells; circulating miRNAs; kidney; tumor plasticity