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

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.

miR-204 inhibits the proliferation and invasion of renal cell carcinoma by inhibiting RAB22A expression

“…Consistent with the statistical result of Wotschofsky et al from GSE37989 in GEO database (24) (Fig. 1A), real-time PCR indicated that miR-204 expression was markedly downregulated in 90% (59/65) of the RCC tissues (P<0.0001; Fig.…”

Cytotoxic activity of sunitinib and everolimus in Caki-1 renal cancer cells is accompanied by modulations in the expression of apoptosis-related microRNA clusters and BCL2 family genes

“…In Caki-1 cells of the present study, miR-143 was undetectable and consequently it could not be evaluated in relation to drug treatment. Though, it is worthwhile mentioning that the expression status of miR-143 in Caki-1 cells has been also reported in renal tissues surgically removed from patients with metastatic RCC [40]. Contrary to miR-143, the expression of miR-145 was evaluated in Caki-1 cells treated with sunitinib or everolimus.…”

Clinical and pathological implications of miRNA in bladder cancer

“…Furthermore, miR20a, miR-106b, miR-141, and miR-205 were found to be upregulated in bladder cancer, 17,18 in contrast to an inverse expression behavior in other locations such as renal or prostate cancer. 18,19 miRNA profiling studies in bladder cancer patient stratification…”