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The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the(More)
Here, we present a unifying hypothesis about how messenger RNAs, transcribed pseudogenes, and long noncoding RNAs "talk" to each other using microRNA response elements (MREs) as letters of a new language. We propose that this "competing endogenous RNA" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the(More)
PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor that antagonizes signaling through the phosphatidylinositol 3-kinase-Akt pathway. We have demonstrated that subtle decreases in PTEN abundance can have critical consequences for tumorigenesis. Here, we used a computational approach to identify miR-22, miR-25, and miR-302 as(More)
MicroRNAs (miRNAs) have recently come into focus as key posttranscriptional modulators of gene expression. In this work, we addressed whether in vitro angiogenesis is an miRNA-regulated process. We performed large-scale analysis of miRNA expression in human umbilical vein endothelial cells (HUVECs) and found that 15 highly expressed miRNAs have the(More)
Tumor cells metastasize to distant organs through genetic and epigenetic alterations, including changes in microRNA (miR) expression. Here we find miR-22 triggers epithelial-mesenchymal transition (EMT), enhances invasiveness and promotes metastasis in mouse xenografts. In a conditional mammary gland-specific transgenic (TG) mouse model, we show that miR-22(More)
MicroRNAs (miRNAs) are short 20-22 nucleotide RNA molecules that act as negative regulators of gene expression via translational repression: they have been shown to play a role in development, proliferation, stress response, and apoptosis. The transcriptional regulator LRF (Leukemia/lymphoma Related Factor) has been shown to prevent p19ARF transcription and(More)
Malignant melanoma is fatal in its metastatic stage. It is therefore essential to unravel the molecular mechanisms that govern disease progression to metastasis. MicroRNAs (miRs) are endogenous non-coding RNAs involved in tumourigenesis. Using a melanoma progression model, we identified a novel pathway controlled by miR-214 that coordinates metastatic(More)
The technology of knockdown of gene expression by synthetic short interfering RNAs (siRNAs) is currently diffused because of its relative simplicity and reliability. Despite the claims that active siRNAs can be easily identified, how to select active siRNAs with high efficiency it is not fully defined. Here, we report that energy profiling can be used in(More)
Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative(More)
RNA interference consists of a sequence specific post-transcriptional gene silencing phenomenon triggered by a double strand RNA molecule homologous to the silenced gene. The dsRNA is cleaved by DICER enzyme in small dsRNA pieces, named short interfering RNAs (siRNAs). These fragments are thereafter associated to RISC complex where the cleavage of target(More)