4.4 Article

Upregulation of FAM50A promotes cancer development

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MEDICAL ONCOLOGY
卷 40, 期 8, 页码 -

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HUMANA PRESS INC
DOI: 10.1007/s12032-023-02072-z

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FAM50A; Prognosis; Immune cell infiltration; DNA damage; Cell proliferation; Cell migration and invasion

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FAM50A is upregulated in multiple types of common cancer tissues and its elevated expression is associated with poor prognosis and immune cell infiltration. Promoter hypomethylation may contribute to FAM50A upregulation. Inhibition of FAM50A expression leads to DNA damage, induction of interferon beta and interleukin-6 expression, and suppression of cancer cell proliferation, invasion, and migration.
FAM50A encodes a nuclear protein involved in mRNA processing; however, its role in cancer development remains unclear. Herein, we conducted an integrative pan-cancer analysis using The Cancer Genome Atlas, Genotype-Tissue Expression, and the Clinical Proteomic Tumor Analysis Consortium databases. Based on the gene expression data from TCGA and GTEx databases, we compared FAM50A mRNA levels in 33 types of human cancer tissues to those in corresponding normal tissues and found that FAM50A mRNA level was upregulated in 20 of the 33 types of common cancer tissues. Then, we compared the DNA methylation status of the FAM50A promoter in tumor tissues to that in corresponding normal tissues. FAM50A upregulation was accompanied by promoter hypomethylation in 8 of the 20 types of tumor tissues, suggesting that promoter hypomethylation contributes to the upregulation of FAM50A in these cancer tissues. Elevated FAM50A expression in 10 types of cancer tissues was associated with poor prognosis in patients with cancer. FAM50A expression was positively correlated with CD4+ T-lymphocyte and dendritic cell infiltration in cancer tissues but was negatively correlated with CD8+ T-cell infiltration in cancer tissues. FAM50A knockdown caused DNA damage, induced interferon beta and interleukin-6 expression, and repressed the proliferation, invasion, and migration of cancer cells. Our findings indicate that FAM50A might be useful in cancer detection, reveal insights into its role in cancer development, and may contribute to the development of cancer diagnostics and treatments.

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