9 research outputs found
Antagonism between the RNA-binding protein Musashi1 and miR-137 and its potential impact on neurogenesis and glioblastoma development
Luteolin inhibits Musashi1 binding to RNA and disrupts cancer phenotypes in glioblastoma cells
The Oncogenic RNA-Binding Protein Musashi1 Is Regulated by HuR via mRNA Translation and Stability in Glioblastoma Cells
IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy, but its role(s) in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and microRNA (miRNA) binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions
Genomic Analyses of Musashi1 Downstream Targets Show a Strong Association with Cancer-related Processes*S⃞
Musashi1 (Msi1) is a highly conserved RNA-binding protein with pivotal
functions in stem cell maintenance, nervous system development, and
tumorigenesis. Despite its importance, only three direct mRNA targets have
been characterized so far: m-numb, CDKN1A, and
c-mos. Msi1 has been shown to affect their translation by binding to
short elements located in the 3′-untranslated region. To better
understand Msi1 functions, we initially performed an RIP-Chip analysis in
HEK293T cells; this method consists of isolation of specific RNA-protein
complexes followed by identification of the RNA component via microarrays. A
group of 64 mRNAs was found to be enriched in the Msi1-associated population
compared with controls. These genes belong to two main functional categories
pertinent to tumorigenesis: 1) cell cycle, cell proliferation, cell
differentiation, and apoptosis and 2) protein modification (including
ubiquitination and ubiquitin cycle). To corroborate our findings, we examined
the impact of Msi1 expression on both mRNA (transcriptomic) and protein
(proteomic) expression levels. Genes whose mRNA levels were affected by Msi1
expression have a Gene Ontology distribution similar to RIP-Chip results,
reinforcing Msi1 participation in cancer-related processes. The proteomics
study revealed that Msi1 can have either positive or negative effects on gene
expression of its direct targets. In summary, our results indicate that Msi1
affects a network of genes and could function as a master regulator during
development and tumor formation