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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2012 > Volume 8 Number 10 > Zofia Wotschofsky1,2*, Julia Liep1,2*, Hellmuth-Alexander Meyer1,3, Monika Jung1, Ina Wagner4, Alexander C. Disch5, Klaus D. Schaser5, Ingo Melcher5, Ergin Kilic6, Jonas Busch1, Steffen Weikert1, Kurt Miller1, Andreas Erbersdobler7, Hans-Joachim Mollenkopf4, Klaus Jung1,2,8✉

Identification of Metastamirs as Metastasis-associated MicroRNAs in Clear Cell Renal Cell Carcinomas

Zofia Wotschofsky1,2*, Julia Liep1,2*, Hellmuth-Alexander Meyer1,3, Monika Jung1, Ina Wagner4, Alexander C. Disch5, Klaus D. Schaser5, Ingo Melcher5, Ergin Kilic6, Jonas Busch1, Steffen Weikert1, Kurt Miller1, Andreas Erbersdobler7, Hans-Joachim Mollenkopf4, Klaus Jung1,2,8✉
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: klaus.jung@charite.de; Tel. ++49-30 450-515041, Fax:++49-30 450-51590.
Abstract :

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.

Date Deposited : 09 Apr 2015 14:50

Last Modified : 09 Apr 2015 14:50

Official URL: http://www.ijbs.com/ms/archive

Volume 8, Number 10, - 2012 , ISSN 1545-1003

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