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


RESULTS
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).


CONCLUSIONS
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.
Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland Baltimore, Baltimore, Maryland, United States of America.
Rania H
RH
Younis
Wei
W
Cao
Ruxian
R
Lin
Ronghui
R
Xia
Zhenqiu
Z
Liu
Martin J
MJ
Edelman
Yuping
Y
Mei
Li
L
Mao
Hening
H
Ren
D000595:Amino Acid Sequence; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D020687:cdc25 Phosphatases / Q000737:chemistry / Q000235:genetics*
D017931:DNA Primers; D020033:Protein Isoforms; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases