RNA-Binding Proteins HuR and PTB Promote the Translation of Hypoxia-Inducible Factor 1α

Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

“…Due to previously published data on the role of HuR in controlling angiogenesis via interactions with VEGF and HIF1α mRNAs, we investigated the relationship between HuR overexpression and these pro-angiogenetic factors. 21,22 There was a statistically significant decrease in VEGF mRNA and protein expression and no increases in HIF1α mRNA or protein expression. As expected, increased HuR expression correlated with increased TSP1 mRNA expression and protein levels.…”

“…We conducted experiments which targeted well known HuR target genes involved in angiogenesis which had previously been described in the literature: thrombospondin 1 (TSP1), VEGF and HIF1α. 21,22,27 We therefore performed real-time PCR to measure mRNA levels of TSP1, VEGF and HIF1α. As seen in Figure 3A, HuR overexpression caused an increase in TSP1 mRNA and protein (Fig.…”

“…[10][11][12][13][14][15][16][17] HuR has been shown to regulate genes in multiple areas of the acquired capabilities model, including two pivotal genes involved in angiogenesis, VEGF and HIF1α. [18][19][20][21][22] Increased HuR cytoplasmic expression directly correlates with severity and aggressiveness of many cancers, including those of the breast. [23][24][25] HuR has been demonstrated to be an important prognostic factor in familial breast cancer patients.…”

miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels

“…HuR stabilizes many target mRNAs (11), likely by antagonizing the effect of decay-promoting TTR-RBPs. Additionally, in some cases HuR promotes target mRNA translation (12)(13)(14), although other times it represses it, particularly when transcripts possess an internal ribosome entry site (IRES) (15). Among the HuR target mRNAs are many that encode proliferation-related proteins, including several that influence cell cycle progression (e.g., cyclins A2, B1, D1, p21, p27), growth factor function (e.g., IGF-1R VEGF, EGF, TGF-␤, GM-CSF), and transcription factor activity (e.g., c-fos, c-myc, c-jun, p53, myogenin, MyoD, ATF-2) (13, 16, reviewed in ref.…”

Transcriptome-Wide Analysis of Regulatory Interactions of the RNA-Binding Protein HuR

“…Table ST3) HuR is known to stabilize many transcripts encoding genes necessary for the immediate response to stress. This is reflected in our data, containing the known HuR target HIF1A (Galbán et al, 2008) and identified by us TXNIP (thioredoxin-interacting protein) and PRKAA1, a kinase that affects HuR localization upon stress (Wang et al, 2002), suggesting a feedback mechanism.…”