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Minichromosome maintenance protein 5 is an important pathogenic factor of oral squamous cell carcinoma.

ABSTRACT: Oral squamous cell carcinoma is one of the most common causes of malignancy-associated death. Early diagnosis of oral squamous cell carcinoma (OSCC) is important in patient treatment and prognostic evaluation. Due to the lack of significant therapeutic benefit, the 5-year survival rate has not improved. Therefore, effective novel markers are needed to improve diagnosis. To determine novel promising diagnostic biomarkers for OSCC, 416 upregulated and 416 downregulated differentially expressed genes were screened from OSCC tissues using an RNA microarray. The results suggested that minichromosome maintenance protein (MCM5) mRNA was significantly overexpressed in OSCC tissues compared with that in adjacent normal tissues. Moreover, silencing of MCM5 expression an OSCC cell line (SCC-15) significantly impaired proliferation and colony formation. Furthermore, negative regulation of the mRNA and protein expression of MCM5 and demonstrated that MCM5 served as a cancer-promoting gene modulating OSCC cell proliferation through induced G2/M phase arrest. In this process, the mRNA expression of cyclin E and cyclin-dependent kinase 2 was downregulated, while p21 expression was upregulated. These results suggested that MCM5 may be an important pathogenic factor of OSCC. High expression levels of MCM5 may serve as a marker for the early diagnosis of OSCC.

SUBMITTER: Hao M

PROVIDER: S-EPMC7439113 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Minichromosome maintenance protein 5 is an important pathogenic factor of oral squamous cell carcinoma.

Hao Miao M Wang Huiyu H Zhang Chu C Li Chunyan C Wang Xiaofeng X

Oncology letters 20200810 4

Oral squamous cell carcinoma is one of the most common causes of malignancy-associated death. Early diagnosis of oral squamous cell carcinoma (OSCC) is important in patient treatment and prognostic evaluation. Due to the lack of significant therapeutic benefit, the 5-year survival rate has not improved. Therefore, effective novel markers are needed to improve diagnosis. To determine novel promising diagnostic biomarkers for OSCC, 416 upregulated and 416 downregulated differentially expressed gen ...[more]

PMID: 32831928

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Project description:Esophageal squamous cell carcinoma (ESCC), the main subtype of esophageal cancer (EC), is a common lethal type of cancer with a high mortality rate. The aim of the present study was to select key relevant genes and identify potential mechanisms involved in the development of ESCC based on bioinformatics analysis. Minichromosome maintenance 6 complex component (MCM6) has been identified to be upregulated in multiple malignancies; however, its contributions to ESCC remain unclear. For the purposes of the present study, four datasets were downloaded from the Gene Expression Omnibus (GSE63941, GSE26886, GSE17351 and GSE77861), and the intersection of the differentially expressed genes was obtained using a Venn diagram. The protein‑protein interaction was then constructed, and the modules were verified by Cytoscape, in which the key genes have a high connectivity degree with other genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were subsequently filtered out to analyze the development of ESCC. MCM6, an upregulated gene, was selected and connected with most of the other genes, for further research validation. The expression levels of MCM6 were then assessed using the Oncomine, GEPIA and UALCAN databases and validated in both ESCC tissues samples and cell lines by immunohistochemistry and RT‑qPCR. Cell counting kit‑8 (CCK‑8), flow cytometry, wound healing and Transwell assays were used to determine the proliferation, apoptosis, cell cycle, migration and invasion of ESCC cells. A total of 24 genes were identified by a series of bioinformatics analyses and the results revealed that the genes were associated with DNA replication and cell cycle. Experimental validation revealed that MCM6 expression was significantly elevated in both ESCC tissues and cell lines. The results were consistent with those of bioinformatics analysis. Furthermore, the knockdown of MCM6 inhibited cell proliferation, migration and invasion and promoted cell apoptosis, and made cells arrested in S stage. In summary, the findings of bioinformatics analysis provided a novel hypothesis for ESCC progression. In particular, the aberrantly elevated expression of MCM6 is a potential biomarker for ESCC diagnosis and treatment.

Dataset Information

Minichromosome maintenance protein 5 is an important pathogenic factor of oral squamous cell carcinoma.

Publications

Minichromosome maintenance protein 5 is an important pathogenic factor of oral squamous cell carcinoma.

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