Dataset Information

CDC25A(Q110del): a novel cell division cycle 25A isoform aberrantly expressed in non-small cell lung cancer.

ABSTRACT:

Objective

Lung cancer remains number one cause of cancer related deaths worldwide. Cell cycle deregulation plays a major role in the pathogenesis of Non-Small Cell Lung Cancer (NSCLC). CDC25A represents a critical cell cycle regulator that enhances cell cycle progression. In this study we aimed to investigate the role of a novel CDC25A transcriptional variant, CDC25A(Q110del), on the regulation of the CDC25A protein, and its impact on prognosis of NSCLC patients.

Methodology/principal findings

Here we report a novel CDC25A transcript variant with codon 110 (Glutamine) deletion, that we termed CDC25A(Q110del) in NSCLC cells. In 9 (75%) of the 12 NSCLC cell lines, CDC25A(Q110del) expression accounted for more than 20% of the CDC25A transcripts. Biological effects of CDC25A(Q110del) were investigated in H1299 and HEK-293F cells using UV radiation, flowcytometry, cyclohexamide treatment, and confocal microscopy. Compared to CDC25A(wt), CDC25A(Q110del) protein had longer half-life; cells expressing CDC25A(Q110del) were more resistant to UV irradiation and showed more mitotic activity. Taqman-PCR was used to quantify CDC25A(Q110del) expression levels in 88 primary NSCLC tumor/normal tissue pairs. In patients with NSCLC, Kaplan Meier curves showed tumors expressing higher levels of CDC25A(Q110del) relative to the adjacent lung tissues to have significantly inferior overall survival (P = .0018).

Significance

Here we identified CDC25A(Q110del) as a novel transcriptional variant of CDC25A in NSCLC. The sequence-specific nature of the abnormality could be a prognostic indicator in NSCLC patients as well as a candidate target for future therapeutic strategies.

SUBMITTER: Younis RH

PROVIDER: S-EPMC3465328 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

CDC25A(Q110del): a novel cell division cycle 25A isoform aberrantly expressed in non-small cell lung cancer.

Younis Rania H RH Cao Wei W Lin Ruxian R Xia Ronghui R Liu Zhenqiu Z Edelman Martin J MJ Mei Yuping Y Mao Li L Ren Hening H

PloS one 20121005 10

<h4>Objective</h4>Lung cancer remains number one cause of cancer related deaths worldwide. Cell cycle deregulation plays a major role in the pathogenesis of Non-Small Cell Lung Cancer (NSCLC). CDC25A represents a critical cell cycle regulator that enhances cell cycle progression. In this study we aimed to investigate the role of a novel CDC25A transcriptional variant, CDC25A(Q110del), on the regulation of the CDC25A protein, and its impact on prognosis of NSCLC patients.<h4>Methodology/principal ...[more]

PMID: 23071577

Similar Datasets

Project description:Long non?coding RNA (lncRNA) LINC00473 plays a carcinogenic role in a variety of different tumor types. Nevertheless, the mechanisms through which LINC00473 regulates the radiosensitivity of esophageal squamous cell carcinoma (ESCC) cells remains elusive. In the present study, reverse transcription?quantitative PCR was used to quantify the expression of LINC00473, microRNA (miRNA/miR)?497?5p and cell division cycle 25A (CDC25A) in ESCC tissues. The association between LINC00473 expression and the clinicopathological characteristics of patients with ESCC was also assessed. Furthermore, Cell Counting kit?8 and colony formation assays were carried out to monitor the proliferation of ESCC cells exposed to X?ray radiation. A dual?luciferase reporter assay was also conducted to analyze the interaction between LINC00473 and miR?497?5p, as well as the interaction between CDC25A and miR?497?5p. The findings of the present study demonstrated that in ESCC tissues and cells, the expression levels of LINC00473 and CDC25A were significantly upregulated, while the expression of miR?497?5p was downregulated. The high expression level of LINC00473 was associated with a higher T stage, lymph node metastasis stage and a lower tumor differentiation grade in patients with ESCC. Following irradiation, transfection with miR?497?5p mimics reduced the promoting effect of LINC00473 overexpression on ESCC cell proliferation, and partially impeded the resistance of ESCC cells to X?ray radiation induced by LINC00473 overexpression. Moreover, transfection with miR?497?5p inhibitors partially alleviated the inhibitory effects of LINC00473 knockdown on cellular proliferation, and partly reversed the sensitivity of cells to X?ray irradiation induced by LINC00473 knockdown. Furthermore, it was confirmed that miR?497?5p was able to bind LINC00473 and the 3'?untranslated region of CDC25A. On the whole, the findings of the present study demonstrate that LINC00473 reduces the radiosensitivity of ESCC cells by modulating the miR?497?5p/CDC25A axis.

Dataset Information

CDC25A(Q110del): a novel cell division cycle 25A isoform aberrantly expressed in non-small cell lung cancer.

Objective

Methodology/principal findings

Significance

Publications

CDC25A(Q110del): a novel cell division cycle 25A isoform aberrantly expressed in non-small cell lung cancer.

Similar Datasets

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