Ricerc@Sapienza

A key challenge for a relevant advance in ccRCC management could derive from a deeper molecular biology characterization of these neoplasms. Recently, we evidenced that miR-210-3p is deregulated in ccRCC tissues and highlighted this miRNA as a potential urine biomarker useful in ccRCC management. MiR-210 was previously described as the major hypoxamir under the regulation of HIF-1alpha and the identification of HIF-1alpha/miR-210-3p-associated pathway could greatly improve not only our knowledge on ccRCC cell growth regulation, cell invasion and metastasis but also lead to the identification of novel clinical and therapeutic targets for ccRCC management.

Aims: i) evaluation of clinical relevance of HIF-1alpha/miR-210-3p-associated pathway in ccRCC management; ii) characterization of HIF-1alpha/miR-210-3p-associated pathway contribution to ccRCC phenotype and drug sensitivity.

Research plan: to explore the contribution of the HIF-1alpha/miR-210-associated pathway in promoting ccRCC phenotype we will focus our attention to metalloproteinase (MMPs) and their tissue inhibitors (TIMPs) that recently were described in relation with this pathway. The major points of our research plan are: i) analysis of HIF-1alpha, miR-210-3p, MMP-9, MMP-2, TIMP-1 and TIMP-2 expression level in neoplastic tissues, peritumoral normal parenchyma and serum and urine of patients diagnosed with ccRCC, and evaluation of associations existing between these factors and clinical outcome; ii) evaluation of HIF-1alpha, miR-210-3p, MMP-9, MMP-2, TIMP-1 and TIMP-2 contribution to ccRCC tumorigenesis; iii) evaluation of the functional relevance of HIF-1alpha/miR-210-3p-associated pathway in the response to conventional cytotoxic drugs treatments.

The identification of HIF-1alpha/miR-210-3p-associated pathway contribution to ccRCC phenotype may be relevant to pave the way for the identification of novel biomarkers for ccRCC management and to design innovative clinical approaches in this tumor.