ABSTRACT
Background: Egl-9 family hypoxia-inducible factor 3 (EGLN3) is involved in the regulation of tumor microenvironment and tumor progression. However, its biological function and clinical significance in various cancers remain unclear. Methods: RNA-seq, immunofluorescence, and single-cell sequencing were used to investigate the expression landscape of EGLN3 in pan-cancer. The TISCH2 and CancerSEA databases were used for single-cell function analysis of EGLN3 in tumors. TIMER2.0 database was used to explain the relationship between EGLN3 expression and immune cell infiltration. In addition, the LinkedOmics database was used to perform KEGG enrichment analysis of EGLN3 in pan-cancer. siRNA was used to silence gene expression. CCK8, transwell migration assay, flow cytometry analysis, RT-PCR, and western blotting were used to explore biological function of EGLN3. Results: The results showed that EGLN3 was highly expressed in a variety of tumors, and was mainly localized to the cytosol. EGLN3 expression is associated with immunoinfiltration of a variety of immune cells, including macrophages in the tumor immune microenvironment and tumor-associated fibroblasts. Functional experiments revealed that EGLN3 knockdown could inhibit cell proliferation, migration, and promote cell apoptosis. In addition, we found that Bax expression was up-regulated and Bcl-2 expression was down-regulated in the si-EGLN3 group. Taken together, as a potential oncogene, EGLN3 is involved in the regulation of tumor malignant process, especially tumor cell apoptosis. Conclusion: We comprehensively investigated the expression pattern, single-cell function, immune infiltration level and regulated signaling pathway of EGLN3 in pan-cancer. We found that EGLN3 is an important hypoxia and immune-related gene that may serve as a potential target for tumor immunotherapy.
ABSTRACT
BACKGROUND: During mitosis and meiosis, centromere proteins (CENPs) play a key role in proper chromosome segregation. Abnormal expression of CENPs leads to chromosome instability, which is the main cause of tumorigenesis. METHODS: To elucidate the functional characteristics of CENPs in pan-cancer, we comprehensively analyzed the expression landscape of CENPs and their relationships with patient survival, genomic alterations, tumor immunity, tumor microenvironment, and anticancer drug sensitivity. The expression patterns and signaling pathways of CENPs were identified through multiple bioinformatics mining and experimental verification. GEPIA2 and PrognoScan were implemented to evaluate the prognostic value of CENPs. The molecular functions of CENPs in pan-cancer were comprehensively assessed using cBioPortal, GSCA, ImmuCellAI, CellMiner, the ROC plotter tool and TIDE. RESULTS: The results showed that CENPs were upregulated in most tumors compared with normal tissues. We confirmed this conclusion by immunohistochemistry and real-time quantitative PCR. Survival analysis revealed a significant association between high CENP expression and a poor prognosis. CENP expression is related to genome alterations, copy number variation, single nucleotide variation and methylation. Among CENP family genes, CENPF and CENPE are mutated at high frequencies in various tumors, while CENPM and CENPA are less frequently mutated. Furthermore, CENPs regulate the tumor mutational burden, stemness, and microsatellite instability, and are associated with tumor immunity. Most importantly, we revealed that CENP family gene expression was correlated with chemosensitivity and immunotherapy responses. CONCLUSION: These findings may clarify the role of CENPs in cancer progression and antitumor drug sensitivity and provide evidence for CENPs as a potential target in pan-cancer.
ABSTRACT
To obtain novel insights into the tumor biology and therapeutic targets of LUAD, we performed a comprehensive analysis of the KCTD family genes. The expression patterns and clinical significance of the KCTD family were identified through multiple bioinformatics mining. Moreover, the molecular functions and potential mechanisms of differentially expressed KCTDs were evaluated using TIMER 2.0, cBioPortal, GeneMANIA, LinkedOmics and GSEA. The results indicated that the mRNA and protein expression levels of KCTD9, KCTD10, KCTD12, KCTD15 and KCTD16 were significantly decreased in LUAD, while those of KCTD5 were significantly increased. High KCTD5 expression was significantly associated with advanced tumor stage, lymph node metastasis, TP53 mutation and poor prognosis. In addition, KCTD5 was positively correlated with CD8 + T cell, neutrophil, macrophage and dendritic cell infiltration. Additionally, KCTDs demonstrate promising prospects in the diagnosis of LUAD. Importantly, high KCTD5 expression was enriched in signaling pathways associated with the malignant progression of tumors, including the inflammatory response, the IL6/JAK/STAT3 signaling pathway, EMT and hypoxia. Further association analysis showed that KCTD5 was positively correlated with hypoxia-related genes such as HIF1. Overall, KCTDs can be used as molecular targets for the treatment of LUAD, as well as effective molecular biomarkers for diagnosis and prognosis prediction.
