Abstract
Abstract Background: MiRNAs are regulators of gene expression in tumorigenesis and progression. To identify miRNAs associated with metastasis miRNA expression in distant metastases was compared to primary clear cell renal cell carcinoma (ccRCC). Material and methods: Total RNA of 27 primary ccRCC samples and 25 distant metastases (lung, bone and brain) was isolated from formalin-fixed paraffin-embedded (FFPE) samples Microarray analyses were performed for a global miRNA expression profiling. Results were validated by qPCR. For miRNA target identification a ccRCC cell line (786-O) was transfected with miRNAs differently expressed in metastatic primary tumors and metastases. Results: We identified 9 miRNAs (including miR-30c and miR-126) with a similar expression in metastatic primary ccRCC and distant metastases from different metastatic sites compared to non-metastatic primary ccRCC. 11 miRNAs (including miR-10b and miR-204) were differently expressed in distant metastases compared to primary ccRCC. Furthermore, each metastatic site is characterized by a specific miRNA signature. Results were verified on selected miRNAs using qPCR. In vitro studies identified potential miRNA targets and associated metastasis related pathways. Discussion: These data suggest that miRNAs play an important role in metastatic processes of ccRCC. Furthermore, our results regarding different metastatic sites suggest two important statements. Specific miRNAs characterize distant metastases in general. On the other hand, miRNA expression is associated with specific conditions at different metastatic sites. Thus, the data presented in this study give the base for a better understanding of the involvement of miRNAs as regulators of metastasis which opens new possibilities for new targeted therapy options. Citation Format: Joana Heinzelmann, Franzsika Stolzenbach, Robert Schneeweiss, Ulrike Wickmann, Sophie Baumgart, Mieczyslaw Gajda, Michael Stöckle, Kerstin Junker. Specific miRNA signatures characterize different metastatic sites in clear cell renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1493. doi:10.1158/1538-7445.AM2014-1493
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