Expression and clinical significance of centrosomal protein 55 in T-cell lymphoma

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Date: January-March 2018
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 2,609 words
Lexile Measure: 1440L

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Byline: Yangyang. Xu, Xiangxiang. Zhou, Ying. Li, Ya. Zhang, Xin. Wang

Context: T-cell lymphomas (TCLs) have been heterogeneous lymphoid malignancies with aggressive clinical phenotype and poor prognosis. Centrosomal protein 55 (CEP55) played a critical role in cytokinesis and served as a centrosome- and midbody-associated protein. Previous studies have reported the overexpression and clinical significance of CEP55 in various human malignancies, but the exact biological roles of CEP55 in TCLs remained unclear. Aims: In this study, we aimed to evaluate the CEP55 expression in patients with TCL and reactive hyperplasia of lymph nodes. The correlation between CEP55 levels and clinical characteristics was also explored for TCL patients. For further investigation, the cell viability of TCL cell lines after CEP55 inhibition was also assessed. Subjects and Methods: Immunohistochemistry was applied to assess the elevated level of CEP55 in TCLs. After siRNA treatment, cell viability and apoptotic rate of TCL cell lines were observed with CCK-8 assay and flow cytometry, respectively. Statistical Analysis: The Pearson's Chi-square test or Fisher's exact test was applied to analyze the correlations between CEP55 overexpression and clinical characteristics. All statistical tests were two-sided, and P < 0.05 was considered to be statistically significant. Results: CEP55 was upregulated in TCL patients and significantly correlated with Ki-67 label index. Consistently, cell viability was decreased, and apoptosis was increased after the suppression of CEP55 in TCL cell lines. Conclusions: These results suggested that target CEP55 would be a novel therapeutic strategy for the TCL.

Introduction

T-cell lymphomas (TCLs) have been heterogeneous diseases of lymphoid malignancies. TCLs appeared to be more aggressive with a worse prognosis compared with that of B-cell lymphomas.[1],[2] However, the etiology and uniformed therapeutic regimen remained to be explored. Increasing number of studies showed that deregulations of signaling pathways, including PI3K/AKT pathway, were critical events in TCLs pathogenesis.[3],[4] Therefore, exploring and unveiling specific molecules contributing to signaling pathways and tumorigenesis has become an attractive topic for its significance in the treatment of TCLs.

Centrosomal protein 55 (CEP55) has been identified and characterized a decade ago. CEP55 was a centrosome- and midbody-associated protein and played a crucial role in cytokinesis, during which two daughter cells were separated physically then finishing the cell division process.[5] CEP55 overexpression has been identified in mRNA microarray expression profiles of many human cancers, resulting in the accumulation of unstable multinucleated cells, which tended to tumor genesis.[6] Previous studies have shown that overexpression of CEP55 was associated with increased cell migration and invasion, whereas apoptosis was significantly increased with the inhibition of CEP55.[7]

The analysis on various tumors revealed that several pathways were dysregulated due to abundant CEP55.[8],[9] One of the major prosurvival pathways involving CEP55 was the PI3K/AKT pathway. PI3K phosphorylated phosphatidylinositol 4,5-bisphosphate (PIP2), converted PIP2 to phosphatidylinositol 3,4,5 trisphosphate (PIP3), and then stimulated the activation of AKT.[10],[11] AKT played diverse roles in cell cycle, angiogenesis, and cell survival. Overactivation of AKT was mainly achieved through the mutation of PIK3CA in multiple cancers.[12] CEP55 was reported to bind PIK3CA, and AKT activation would be...

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Gale Document Number: GALE|A530723051