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.