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Growth factor dependent regulation of centrosome function and genomic instability by HuR.

Filippova N, Yang X, Nabors LB - Biomolecules (2015)

Bottom Line: This process is regulated by tyrosine phosphorylation of HuR and is abolished by mutating tyrosine residues.HuR is overexpressed in tumor samples from patients with glioblastoma and associated with a reduced survival.These findings suggest HuR plays a significant role in centrosome amplification and genomic instability, which contributes to a worse disease outcome.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Alabama at Birmingham, 510 20th Street South, FOT 1020, Birmingham, AL 35209, USA. as1999@uab.edu.

ABSTRACT
The mRNA binding protein HuR is over expressed in cancer cells and contributes to disease progression through post-transcriptional regulation of mRNA. The regulation of HuR and how this relates to glioma is the focus of this report. SRC and c-Abl kinases regulate HuR sub-cellular trafficking and influence accumulation in the pericentriolar matrix (PCM) via a growth factor dependent signaling mechanism. Growth factor stimulation of glioma cell lines results in the associate of HuR with the PCM and amplification of centrosome number. This process is regulated by tyrosine phosphorylation of HuR and is abolished by mutating tyrosine residues. HuR is overexpressed in tumor samples from patients with glioblastoma and associated with a reduced survival. These findings suggest HuR plays a significant role in centrosome amplification and genomic instability, which contributes to a worse disease outcome.

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The expression of HuR, SRC, and Abl-1 in brain tumor and control samples. (A) Illustration of expression of HuR, SRC, and Abl-1 proteins in samples from brain tumor and control brain tissue. (B) Left—Profiles of HuR and Abl-1 mRNAs expression in different groups of brain tumors compared to non-tumor group. The data was obtained from Rembrandt National Cancer Institute database. * represents non-tumor control brain. Right—Illustrates Kaplan-Meier survival plot for GBM patients with different levels of ELAVL1 gene expression (201727—Taqman probe for ELAVL1 gene detection). The survival curves represent the following groups: red—up regulated (192), yellow—intermediate (150), green—down regulated (1), blue—all (343). Log-rank p-value for significance of different survival between up-regulated versus intermediate groups is 1.929E-7 (Rembrandt National Cancer Institute data base).
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biomolecules-05-00263-f008: The expression of HuR, SRC, and Abl-1 in brain tumor and control samples. (A) Illustration of expression of HuR, SRC, and Abl-1 proteins in samples from brain tumor and control brain tissue. (B) Left—Profiles of HuR and Abl-1 mRNAs expression in different groups of brain tumors compared to non-tumor group. The data was obtained from Rembrandt National Cancer Institute database. * represents non-tumor control brain. Right—Illustrates Kaplan-Meier survival plot for GBM patients with different levels of ELAVL1 gene expression (201727—Taqman probe for ELAVL1 gene detection). The survival curves represent the following groups: red—up regulated (192), yellow—intermediate (150), green—down regulated (1), blue—all (343). Log-rank p-value for significance of different survival between up-regulated versus intermediate groups is 1.929E-7 (Rembrandt National Cancer Institute data base).

Mentions: To verify that the expression and possible interaction of HuR with Abl-1 and SRC kinases is not restricted to U251 cells, we analyzed Abl-1, SRC, and HuR expression in eight brain tumor samples and seven samples of control brain tissue (Figure 8A). We also checked five additional established glioma cell lines. We confirm over-expression of HuR and Abl-1 in the majority of tumor samples and cell lines compared to control brain tissues (Figure 8A). In addition, we noticed the unique pattern of Abl-1 expression (cleavage or isoforms) in tumor samples, which was different from the Abl-1 pattern in samples of control brain tissues (Figure 8A). The HuR and Abl-1 protein expression data is in agreement with the profiles of mRNA expression of HuR (ELAVL1) and Abl-1 genes provided in the Rembrandt National Cancer Institute database (Figure 8B). Figure 8B illustrates a significant increase (over two fold) in HuR and Abl-1 mRNA expression in groups of different types of brain tumors compared to the normal (non tumor) group. In addition, over-expression of HuR is associated with decreased patient survival as shown in the Kaplan-Meir survival curves (Figure 8B-right).


Growth factor dependent regulation of centrosome function and genomic instability by HuR.

Filippova N, Yang X, Nabors LB - Biomolecules (2015)

The expression of HuR, SRC, and Abl-1 in brain tumor and control samples. (A) Illustration of expression of HuR, SRC, and Abl-1 proteins in samples from brain tumor and control brain tissue. (B) Left—Profiles of HuR and Abl-1 mRNAs expression in different groups of brain tumors compared to non-tumor group. The data was obtained from Rembrandt National Cancer Institute database. * represents non-tumor control brain. Right—Illustrates Kaplan-Meier survival plot for GBM patients with different levels of ELAVL1 gene expression (201727—Taqman probe for ELAVL1 gene detection). The survival curves represent the following groups: red—up regulated (192), yellow—intermediate (150), green—down regulated (1), blue—all (343). Log-rank p-value for significance of different survival between up-regulated versus intermediate groups is 1.929E-7 (Rembrandt National Cancer Institute data base).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384122&req=5

biomolecules-05-00263-f008: The expression of HuR, SRC, and Abl-1 in brain tumor and control samples. (A) Illustration of expression of HuR, SRC, and Abl-1 proteins in samples from brain tumor and control brain tissue. (B) Left—Profiles of HuR and Abl-1 mRNAs expression in different groups of brain tumors compared to non-tumor group. The data was obtained from Rembrandt National Cancer Institute database. * represents non-tumor control brain. Right—Illustrates Kaplan-Meier survival plot for GBM patients with different levels of ELAVL1 gene expression (201727—Taqman probe for ELAVL1 gene detection). The survival curves represent the following groups: red—up regulated (192), yellow—intermediate (150), green—down regulated (1), blue—all (343). Log-rank p-value for significance of different survival between up-regulated versus intermediate groups is 1.929E-7 (Rembrandt National Cancer Institute data base).
Mentions: To verify that the expression and possible interaction of HuR with Abl-1 and SRC kinases is not restricted to U251 cells, we analyzed Abl-1, SRC, and HuR expression in eight brain tumor samples and seven samples of control brain tissue (Figure 8A). We also checked five additional established glioma cell lines. We confirm over-expression of HuR and Abl-1 in the majority of tumor samples and cell lines compared to control brain tissues (Figure 8A). In addition, we noticed the unique pattern of Abl-1 expression (cleavage or isoforms) in tumor samples, which was different from the Abl-1 pattern in samples of control brain tissues (Figure 8A). The HuR and Abl-1 protein expression data is in agreement with the profiles of mRNA expression of HuR (ELAVL1) and Abl-1 genes provided in the Rembrandt National Cancer Institute database (Figure 8B). Figure 8B illustrates a significant increase (over two fold) in HuR and Abl-1 mRNA expression in groups of different types of brain tumors compared to the normal (non tumor) group. In addition, over-expression of HuR is associated with decreased patient survival as shown in the Kaplan-Meir survival curves (Figure 8B-right).

Bottom Line: This process is regulated by tyrosine phosphorylation of HuR and is abolished by mutating tyrosine residues.HuR is overexpressed in tumor samples from patients with glioblastoma and associated with a reduced survival.These findings suggest HuR plays a significant role in centrosome amplification and genomic instability, which contributes to a worse disease outcome.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Alabama at Birmingham, 510 20th Street South, FOT 1020, Birmingham, AL 35209, USA. as1999@uab.edu.

ABSTRACT
The mRNA binding protein HuR is over expressed in cancer cells and contributes to disease progression through post-transcriptional regulation of mRNA. The regulation of HuR and how this relates to glioma is the focus of this report. SRC and c-Abl kinases regulate HuR sub-cellular trafficking and influence accumulation in the pericentriolar matrix (PCM) via a growth factor dependent signaling mechanism. Growth factor stimulation of glioma cell lines results in the associate of HuR with the PCM and amplification of centrosome number. This process is regulated by tyrosine phosphorylation of HuR and is abolished by mutating tyrosine residues. HuR is overexpressed in tumor samples from patients with glioblastoma and associated with a reduced survival. These findings suggest HuR plays a significant role in centrosome amplification and genomic instability, which contributes to a worse disease outcome.

Show MeSH
Related in: MedlinePlus