Minichromosome Maintenance Protein 10 As A Marker For Proliferation And Prognosis In Lung Cancer

INTERNATIONAL JOURNAL OF ONCOLOGY(2019)

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摘要
DNA replication is a vital process in cell division where anomalies can lead to tumorigenesis. Minichromosome maintenance complex component 10 (MCM10) plays a crucial role in this process. However, the role of MCM10 in lung cancer pathogenesis remains to be elucidated. In current study, using the publicly available lung cancer Gene Expression Omnibus (GEO) datasets, and Oncomine and the Cancer Genome Atlas databases, an increased expression of MCM10 was found in lung cancer tissues compared to normal lung tissues. The high expression of MCM10 was subsequently validated in clinical specimens by reverse transcription-quantitative PCR and immunohistochemistry. Analysis of the GEO datasets revealed that the high MCM10 expression was significantly associated with early and late recurrence, pathological stage and worse overall survival (OS). Cox's proportional hazards regression analyses revealed that MCM10 expression was an independent risk factor for poor OS and worse recurrence-free survival both in univariate and multivariate analysis. Furthermore, the increased expression of MCM10 was enriched in cell cycle-related processes, while in vitro transfection with small interfering RNA targeting MCM10 significantly suppressed cell viability, clone formation and induced G1 phase arrest in A549 and H661 cell lines by regulating the expression of cyclin D1 (CCND1). In addition, the current results indicated a combined effect of MCM10-CCND1 in predicting the prognosis of lung cancer patients. Altogether, the present study provided a novel potential molecular mechanism of lung cancer progression and may aid in development of novel treatment strategies.
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关键词
minichromosome maintenance protein 10, lung cancer, prognosis, proliferation, biomarker
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