Recently long non-coding RNAs (lncRNA) have emerged as new gene regulators and prognostic markers in several cancers including renal cell carcinoma (RCC). In this study, we investigated the contributions of the lncRNA MALAT1 in RCC with a specific focus on its transcriptional regulation and its interactions with Ezh2 and miR-205. We found that MALAT1 expression was higher in human RCC tissues where it was associated with reduced patient survival. MALAT1 silencing decreased RCC cell proliferation and invasion and increased apoptosis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased while beta-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. Lastly, MALAT1 bound Ezh2 and oncogenesis facilitated by MALAT1 was inhibited by Ezh2 depletion, thereby blocking epithelial-mesenchyme transition via E-cadherin recovery and beta-catenin downregulation. Overall, our findings illuminate how overexpression of MALAT1 confers an oncogenic function in RCC that may offer a novel theranostic marker in this disease.

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Background MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of approximately 30% of all human genes. They play important roles in numerous cellular processes including development, proliferation, and apoptosis. It is currently believed that miRNAs elicit their effect by silencing the expression of target genes. Here we show that microRNA-205 (miR-205) induces the expression of IL24 and IL32 tumor suppressor genes by targeting specific sites in their promoters. Methods Methods used in this study include transfection of small RNAs, quantitative-real-time-PCR, in-situ hybridization, fluorescence labeled in-situ hybridization, cell cycle, apoptosis, cell viability, migratory, clonability and invasion assays, immunoblotting, luciferase reporter, nuclear run-on and chromatin immunoprecipitation assays. Results Our results revealed that miR-205 is silenced in prostate cancer. Its re-expression induced apoptosis and cell cycle arrest. It also impaired cell growth, migration, clonability and invasiveness of prostate cancer cells. MicroRNA-205 induced tumor suppressor genes IL24 and IL32 at both mRNA and protein levels. Induction of in-vitro transcription and enrichment of markers for transcriptionally active promoters in IL24 and IL32 genes was observed in response to miR-205. Conclusion In this study we identify a new function for miR-205 to specifically activate tumor suppressor genes by targeting specific sites in their promoters. These results corroborate a new function that miRNAs have in regulating gene expression at the transcriptional level. The specific activation of tumor suppressor genes (e.g., IL24, IL32) or other dysregulated genes by microRNAs may contribute to the novel therapeutic approach in the treatment of prostate cancer.