In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6_suppl ( 2013-02-20), p. 385-385
Abstract:
385 Background: miRNAs play a crucial rule in tumor progression and metastasis. We previously identified miR-192, miR-194 and miR-215 to be down-regulated in metastatic compared to primary clear cell renal cell carcinoma (ccRCC). In this work, we examine the role of miR-192, miR-194, and miR-215 in RCC progression and aggressiveness. Methods: We examined the role of these three miRNAs on tumor cell migration and invasion abilities using RCC cell line models. We performed target prediction analysis and experimentally validated the targets using independent approaches. In addition, we examined the clinical utility of miR-215 as a potential prognostic marker in RCC by measuring miR-215 expression using qRT-PCR in 61 formalin-fixed paraffin-embedded tissues from primary ccRCC and correlated the expression levels with clinical outcome. Results: Restoration of miR-192, miR-194, and miR-215 expression decreased cell migration and invasion in RCC cell lines. Target prediction analysis identified three potential targets of these miRNAs; MDM2, TYMS, and SIP1/ZEB2. We validated the miRNA-target interaction experimentally using three approaches. First by measuring the effect of miRNA overexpression on mRNA and protein levels of the predicted target, then by measuring the effect of miRNA overexpression on a luciferase signal of a vector containing the 3’UTR of the predicted target, and finally, by validating these interactions in vivoby examining the presence of an inverse correlation between miRNA changes and the expression levels of their targets on clinical specimens. In 61 patients with resected ccRCC tumors, we found that low miR-215 expression in the primary was associated with a significantly reduced recurrence-free survival. (26.4 vs. 49.2 months, respectively, p = 0.0320). Conclusions: Our analysis showed that miR-192, miR-194, and miR-215 are involved in RCC metastasis and that miR-215 predicts for recurrence in patients with resected RCC. Our findings pave the way to the clinical use of miRNAs as prognostic markers and potential therapeutic targets.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.6_suppl.385
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
