Mp85-11 genetic deletion of sav1 enhances proliferation and nuclear irregularity in renal tubular epithelial cells

INTRODUCTION AND OBJECTIVES: There are more than 200,000 cases of renal cell carcinoma (RCC) each year in the world, accounting for approximately 2% of all cancers. RCC clear cell type (ccRCC) is the most common subtype of RCC and accounts for 75 to 80% of the cases with highest rates of local invasion, development of metastasis and mortality. New target therapy is based on antiangiogenic antibodies and molecules, changing the course of the disease, but the results so far are disappointing. Our aim is to study miRNAs and their target genes related to angiogenesis in ccRCC trying to bring some new knowledge to the molecular pathways related to the disease METHODS: The expression levels of miRNAs miR-99a, 99b, 100; 199a; 106a; 106b; 29a; 29b; 29c; 126; 200a, 200b and their respective target genes: mTOR, HIF1-a, VHL, PDGF, VEGF, VEGFR1 and VEGFR2 were evaluated using qRT-PCR.in snap-frozen tumor tissue samples from 56 patients diagnosed with ccRCC and 5 samples of benign renal tissue as control. The results were related to tumor size, Fuhrman nuclear grade and microvascular invasion, considering the risk criteria proposed by Dall’Oglio et al. (2007). RESULTS: We found an underexpression of the most genes except the VEGFA and PDGF, while the analysis of miRNAs showed underexpression only the miR 199a, 100 and 126. We compared the expression of genes with their possible regulatory miRNAs, and we found that mTOR was underexpressed while miR99a was overexpressed in most samples. This relationship also occurs between VEGFA and miR126 and between miRNAs 106a, 106b, and their target gene VHL. Considering the risk groups the overexpression of miR200b was associated with high-risk patients (p 1⁄4 0.01) and the overexpression of miR126 was associated with lower Fuhrman grade (I-II) (p 1⁄4 0.03). CONCLUSIONS: Our results show that in ccRCC there is an unbalance in the expression of genes and miRNAs related to angiogenesis and cell proliferation and survival. Furthermore with our findings we can speculate the role of miR200b and miR126 in the prognostic of ccRCC. We believe that the relationship between miRNAs and their respective genes should be more profoundly searched as markers and possible therapeutic agents in this neoplasia.