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Meta-analysis of the expression of the mitosis-related gene Fam83D.

ABSTRACT: The family with sequence similarity 83, member D (Fam83D) encodes a mitotic spindle-associated protein. Its knockdown results in shorter spindles that fail to organize a correct metaphase plate. In this study, we demonstrated that Fam83D is coexpressed with well-known mitotic genes. Pathway analysis results also showed that cell cycle- and mitosis-related pathways are enriched with Fam83D-coexpressed genes. Furthermore, Fam83D is differentially expressed in various types of cancers. The results presented in this study suggest that Fam83D may be an important molecule for mitotic progression and equal segregation of chromosomes. Since the molecules that are involved in these mechanisms are crucial for mitosis as well as carcinogenesis, Fam83D should be considered as a novel regulator of mitosis and a putative carcinogenesis-related gene.

SUBMITTER: Varisli L

PROVIDER: S-EPMC3506721 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Meta-analysis of the expression of the mitosis-related gene Fam83D.

Varisli Lokman L

Oncology letters 20120920 6

The family with sequence similarity 83, member D (Fam83D) encodes a mitotic spindle-associated protein. Its knockdown results in shorter spindles that fail to organize a correct metaphase plate. In this study, we demonstrated that Fam83D is coexpressed with well-known mitotic genes. Pathway analysis results also showed that cell cycle- and mitosis-related pathways are enriched with Fam83D-coexpressed genes. Furthermore, Fam83D is differentially expressed in various types of cancers. The results ...[more]

PMID: 23205133

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Project description:Background: The family with sequence similarity 83 member D (FAM83D) protein is known to play a significant role in many human diseases. However, its role in cancer remains ambiguous. This study aimed to investigate the function of FAM83D in a pan-cancer analysis, with a special focus on breast cancer. Methods: Samples were collected from The Cancer Genome Atlas (TCGA) and used for bioinformatic analysis. Datasets from the Gene Expression Omnibus (GEO) and Genotype-Tissue Expression (GTEx) databases were also analyzed for verification. The potential value of FAM83D as a prognostic and diagnostic biomarker was visualized through R software. The "survival" and "GSVA" package were used for univariate, multivariate and pathway enrichment analyseis. We further analyzed the CancerSEA databases and TISIDB websites for single-cell and immune-related profiling. Lastly, we validated those data in vitro using quantitative reverse transcriptase-polymerase chain reaction (RT‒qPCR), cell counting kit-8 (CCK-8), transwell, flow cytometry, and tumorigenicity assays in a murine cell line model. Results: The expression of FAM83D in tumor samples was significantly higher than in normal tissues for most cancer types in the datasets. We confirmed this finding using RT‒qPCR in a breast cancer cell line. Analysis of multiple datasets suggests that overall survival (OS) was extremely poor for breast cancer patients with high FAM83D expression. The CCK-8 assay demonstrated that MCF-7 cell proliferation was inhibited after genetic silencing of FAM83D. Transwell assay showed that knockdown of FAM83D significantly inhibited the invasion and migration ability of MCF-7 cells compared to the control. The results of flow cytometry showed that silencing FAM83D could block the G1 phase of MCF-7 cells compared with negative groups. The tumorigenicity assay in nude mice indicated that the tumorigenic ability to silence FAM83D decreased compared. Conclusion: Results suggest that FAM83D expression can serve as a valuable biomarker and core gene across cancer types. Furthermore, FAM83D expression is significantly associated with MCF-7 cell proliferation and thus may be a prospective prognostic biomarker especially for breast cancer.

Project description:Background OIP5 is found at the centromere and plays an important role in recruiting centromere protein-A (CENP-A) through interacting with Holliday junction recognition protein during cell mitosis. OIP5 is considered to be a cancer-testis specific gene, but its function in tumor development remains unclear. Increased expression of OIP5 has been reported in testis as well as in different cancers; however, the underlying mechanisms remain obscure. Methods Data were collected from the Genotype-Tissue Expression project, the Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas (TCGA) to analyze the effect of OIP5 in many common cancers. Analyses of the differential expression of OIP5 and its relationships with prognosis, the tumor microenvironment, immune infiltration, immune regulation, neoantigen production, and genomic stability in various cancers were performed using R software. Results Expression of OIP5 was significantly increased in 34 common tumor types compared with matched healthy samples; however, no significant increases were observed in pheochromocytoma and paraganglioma or kidney chromophobe. Elevated OIP5 expression predicted dismal overall survival in 14 tumors. The function of OIP5 in tumor-infiltrating immune cells (TIIC) was analyzed, and OIP5 might inhibit TIIC infiltration in the tumor microenvironment; a positive correlation was found in thymoma, while a negative correlation was observed in lung squamous cell carcinoma and lung adenocarcinoma. High OIP5 expression was related to immune regulation and neoantigen production, particularly in terms of the levels of immune regulatory molecules and the number of neoantigens produced in lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma. It was also associated with increased cell genome instability in lung adenocarcinoma. Gene set enrichment analysis revealed potential critical effects of OIP5 on the cell cycle, base excision repair, homologous recombination, DNA replication, the p53 signaling pathway, and mismatch repair pathways. Conclusions High expression of OIP5 is found in many common tumors and predicts a dismal prognostic outcome. The gene is an important recruitment factor for CENP-A and may promote tumor progression by affecting the tumor immune microenvironment and genomic stability. Therefore, OIP5 can serve as a potential candidate factor to predict cancer prognosis and guide the use of therapeutics.

Dataset Information

Meta-analysis of the expression of the mitosis-related gene Fam83D.

Publications

Meta-analysis of the expression of the mitosis-related gene Fam83D.

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