Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ERBB-2 overexpression is associated with the development and progression of cancer and mediates its resistance to therapy. It has been suggested that post-transcriptional mechanisms control the overexpression of ERBB-2 in prostate cancer (PCa). We recently demonstrated that the 3'-untranslated region (3'-UTR) of ERBB-2 mRNA contains two specific target sites for binding of the microRNA miR-331-3p and that miR-331-3p represses ERBB-2 expression and signaling in PCa cells. Here we investigate a U-rich element situated in close proximity to the distal miR-331-3p target site in the ERBB-2 3'-UTR. Specific binding of HuR to this U-rich element promotes ERBB-2 expression in PCa cells. We show that HuR antagonizes the repressive action of miR-331-3p on its distal ERBB-2 3'-UTR target site. These results support a model in which the interplay between RNA-binding proteins and microRNAs controls the post-transcriptional regulation of gene expression and suggest that both HuR and miR-331-3p participate in the overexpression of ERBB-2 observed in some PCas.
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PMID:The RNA-binding protein HuR opposes the repression of ERBB-2 gene expression by microRNA miR-331-3p in prostate cancer cells. 2197 Oct 48

HuR is an ubiquitously expressed RNA-binding protein that stabilizes messenger RNA and regulates translation. This protein has been shown to play an important role in carcinogenesis and cancer progression. P-glycoprotein (P-gp) is the product of the multidrug resistance 1 gene, and the overexpression of P-gp induces multidrug resistance and represents a major obstacle in cancer chemotherapy. The purpose of this study was to determine the expression of HuR and P-gp in human breast cancer tissues and analyze the relationship between HuR or P-gp expression and the clinical-pathological variables and patient outcomes. Immunohistochemistry was used to determine HuR and P-gp expression in 82 human breast cancer tissues and 20 matched adjacent noncancerous tissues. Additionally, 16 benign breast tumor samples were used as controls. The overexpression of cytoplasmic HuR was found in breast cancer but not in the matched adjacent noncancerous tissues or benign breast tumors. The expression levels of cytoplasmic HuR were significantly associated with increased age, high nuclear grade, and the positive expression of the ER, PR, and HER-2/neu. HuR was also associated with the expression of P-gp protein. Furthermore, univariate analysis indicates that patients with high expression levels of cytoplasmic HuR or P-gp had significantly reduced survival compared to patients with low expression levels. A multivariate analysis showed that age at diagnosis, nuclear grade, and cytoplasmic HuR positivity were independent indicators for disease-free survival and overall survival in patients with breast cancer. In conclusion, cytoplasmic HuR expression detected by immunohistochemical staining is a negative prognostic indicator for survival in patients with breast cancer.
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PMID:Cytoplasmic HuR expression correlates with P-gp, HER-2 positivity, and poor outcome in breast cancer. 2360 20

Hepatitis B virus- (HBV-) associated hepatocellular carcinoma (HCC) is the most common type of liver cancer. However, the underlying mechanism of HCC tumorigenesis is very complicated and HBV-encoded X protein (HBx) has been reported to play the most important role in this process. Activation of downstream signal pathways of epidermal growth factor receptor (EGFR) family is known to mediate HBx-dependent HCC tumor progression. Interestingly, HER2 (also known as ErbB2/Neu/EGFR2) is frequently overexpressed in HBx-expressing HCC patients and is associated with their poor prognosis. However, it remains unclear whether and how HBx regulates HER2 expression. In this study, our data showed that HBx expression increased HER2 protein level via enhancing its mRNA stability. The induction of RNA-binding protein HuR expression by HBx mediated the HER2 mRNA stabilization. Finally, the upregulated HER2 expression promoted the migration ability of HBx-expressing HCC cells. These findings deciphered the molecular mechanism of HBx-mediated HER2 upregulation in HBV-associated HCC.
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PMID:Hepatitis B virus X upregulates HuR protein level to stabilize HER2 expression in hepatocellular carcinoma cells. 2471 90