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Expression and Prognostic Value of MCM Family Genes in Osteosarcoma.

ABSTRACT: We performed a detailed cancer VS normal analysis to explore the expression and prognostic value of minichromosome maintenance (MCM) proteinsin human sarcoma. The mRNA expression levels of the MCM family genes in sarcoma were analyzed using data from ONCOMINE, GEPIA and CCLE databases. KEGG database was used to analyze the function of MCM2-7 complex in DNA replication and cell cycle. QRT-PCR and western blot were used to confirm the differential expression of key MCMs in osteosarcoma cell lines. Cell Counting Kit-8 and flow cytometry method were used to detect the cell proliferation and apoptosis of hFOB1.19 cells. The results showed that MCM1-7 and MCM10 were all upregulated in sarcoma in ONCOMINE database. MCM2, and MCM4-7 were highly expressed in sarcoma in GEPIA database. Moreover, all these ten factors were highly expressed in sarcoma cell lines. Furthermore, we analyzed the prognostic value of MCMs for sarcoma in GEPIA and found that MCM2, MCM3, MCM4, and MCM10 are prognostic biomarkers for human sarcoma. Analysis results using KEGG datasets showed that MCM4 and MCM6-7 constituted a core structure of MCM2-7 hexamers. We found that AzadC treatment and overexpression of MCM4 significantly promoted hFOB1.19 cell proliferation and inhibited apoptosis. The present study implied that MCM2-4 and 10 are potential biomarkers for the prognosis of sarcoma. The prognostic role of MCM4 may be attributable to the change in its DNA methylation patterns.

SUBMITTER: Zhou J

PROVIDER: S-EPMC8257954 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Breast cancer (BC) is the most common type of malignancy among females worldwide. Histone modifications, which are the major post-translational modifications, have a significant role in cancer development and prognosis. However, whether histone family genes may serve as potential prognostic biomarkers for BC patients has remained elusive. In the present study, RNA-sequencing data were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes were identified and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analysis was performed. As histone family genes have been reported to be associated with cervical cancer, the present study hypothesized that histone family genes are associated with gynecological tumors. Histone family genes, including histone cluster 1 H1A family member B (HIST1H1B), HIST1H2AJ, HIST1H2AM, HIST1H2BI, HIST1H2BO, HIST1H3B, HIST1H3F, HIST1H3H, HIST1H4C and HIST1H4D, were upregulated and identified as hub genes in the protein-protein interaction network. In addition, Oncomine and the Human Protein Atlas were used to further verify the expression levels of histone gene sets. The PrognoScan database was then used to investigate the association between expression and prognostic value regarding cancer patient survival. The present results indicated that higher expression of histone gene sets was associated with poor overall survival, relapse-free survival and distant metastasis-free survival of BC patients. The differential expression of histone family genes between BC and normal samples was validated by reverse transcription-quantitative PCR. Finally, to determine the clinical role of histone family genes in BC, the correlations between histone family genes expression and clinical characteristics were investigated through data collected from TCGA. Therefore, the present study indicates that histone gene sets may be used as prognostic factors for survival prediction for BC patients.

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Expression and Prognostic Value of MCM Family Genes in Osteosarcoma.

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