Int J Biol Sci 2012; 8(10):1363-1374. doi:10.7150/ijbs.5106
Identification of Metastamirs as Metastasis-associated MicroRNAs in Clear Cell Renal Cell Carcinomas
1. Department of Urology, University Hospital Charité, Berlin, Germany.
2. Berlin Institute for Urologic Research, Berlin, Germany.
3. Institute of Physiology, University Hospital Charité, Berlin, Germany.
4. Max Planck Institute for Infection Biology, Berlin, Germany.
5. Center for Musculoskeletal Surgery, University Hospital Charité, Berlin, Germany.
6. Institute of Pathology, University Hospital Charité, Germany.
7. Institute of Pathology, University Rostock, Germany.
8. Corresponding author: Prof. Dr. Klaus Jung, Department of Urology, University Hospital Charité, Schumannstrasse 20/21, D-10117 Berlin, Germany; E-mail: firstname.lastname@example.org; Tel. ++49-30 450-515041, Fax:++49-30 450-51590.
* These authors contributed equally.
Wotschofsky Z, Liep J, Meyer HA, Jung M, Wagner I, Disch AC, Schaser KD, Melcher I, Kilic E, Busch J, Weikert S, Miller K, Erbersdobler A, Mollenkopf HJ, Jung K. Identification of Metastamirs as Metastasis-associated MicroRNAs in Clear Cell Renal Cell Carcinomas. Int J Biol Sci 2012; 8(10):1363-1374. doi:10.7150/ijbs.5106. Available from http://www.ijbs.com/v08p1363.htm
MicroRNAs (miRNAs) play a pivotal role in cancerogenesis and cancer progression, but their specific role in the metastasis of clear cell renal cell carcinomas (ccRCC) is still limited. Based on microRNA microarray analyses from normal and cancerous samples of ccRCC specimens and from bone metastases of ccRCC patients, we identified a set of 57 differentially expressed microRNAs between these three sample groups of ccRCC. A selected panel of 33 miRNAs was subsequently validated by RT-qPCR on total 57 samples. Then, 30 of the 33 examined miRNAs were confirmed to be deregulated. A stepwise down-regulation of miRNA expression from normal, over primary tumor to metastatic tissue samples, was found to be typical. A total of 23 miRNAs (miR-10b/-19a/-19b/-20a/-29a/-29b/-29c/-100/-101/-126/-127/-130/-141/-143/-145/-148a/-192/-194/-200c/-210/-215/-370/-514) were down-regulated in metastatic tissue samples compared with normal tissue. This down-regulated expression in metastatic tissue in comparison with primary tumor tissue was also present in 21 miRNAs. In cell culture experiments with 5-aza-2'-deoxycytidine and trichostatin A, epigenetic modifications were shown as one reason of this down-regulation. The altered miRNA profiles, comprising newly identified metastasis-associated miRNAs, termed metastamir and the predicted miRNA-target interactions together with the significant correlations of miRNAs that were either lost or newly appeared in the studied sample groups, afford a solid basis for further functional analyses of individual miRNAs in RCC metastatic progression.
Keywords: Renal cell carcinoma, Microarray, RT-qPCR, microRNAs, Metastasis.