Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325015, People's Republic of China.
Med Oncol. 2023 Jul 1;40(8):217. doi: 10.1007/s12032-023-02072-z.
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.
FAM50A 编码一种参与 mRNA 处理的核蛋白；然而，其在癌症发展中的作用尚不清楚。在此，我们使用癌症基因组图谱（TCGA）、基因-组织表达（GTEx）和临床蛋白质组肿瘤分析联盟（CPTAC）数据库进行了综合泛癌症分析。基于 TCGA 和 GTEx 数据库的基因表达数据，我们比较了 33 种人类癌症组织和相应正常组织中的 FAM50A mRNA 水平，发现 FAM50A mRNA 水平在 33 种常见癌症组织中的 20 种中上调。然后，我们比较了肿瘤组织中 FAM50A 启动子的 DNA 甲基化状态与相应正常组织中的状态。在 20 种肿瘤组织中的 8 种中，FAM50A 的上调伴随着启动子低甲基化，这表明启动子低甲基化导致这些癌症组织中 FAM50A 的上调。在 10 种癌症组织中，FAM50A 表达的升高与癌症患者的预后不良相关。FAM50A 在癌症组织中的表达与 CD4+ T 淋巴细胞和树突状细胞的浸润呈正相关，而与 CD8+ T 细胞的浸润呈负相关。FAM50A 的敲低导致 DNA 损伤，诱导干扰素-β和白细胞介素-6 的表达，并抑制癌细胞的增殖、侵袭和迁移。我们的研究结果表明，FAM50A 可能在癌症检测中有用，揭示了其在癌症发展中的作用，并可能有助于癌症诊断和治疗的发展。
