IntroductionNDC80 kinetochore complex component (NUF2) is upregulated and plays an important role in various human cancers. However, the function and mechanism of NUF2 in epithelial ovarian cancer (EOC) remain unclear.MethodsNUF2 expression was detected in EOC tissues and cell lines. The effects of NUF2 downregulation on cell proliferation, migration and invasion in EOC were analyzed by CCK-8 and Transwell assays. Meanwhile, the effect of NUF2 downregulation on tumor growth in vivo was determined by xenograft tumor models. The mechanisms by which NUF2 regulates EOC progression were detected by RNA sequencing and a series of in vitro assays.ResultsWe showed that NUF2 was significantly upregulated in EOC tissues and cell lines, and high NUF2 expression was associated with FIGO stage, pathological grade and poor EOC prognosis. NUF2 downregulation decreased cell proliferation, migration, invasion and tumor growth in nude mice. RNA sequencing studies showed that NUF2 knockdown inhibited several genes enriched in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. Erb-B2 receptor tyrosine kinase 3 (ERBB3) was the key factor involved in both of the above pathways. We found that ERBB3 silencing could inhibit EOC progression and repress activation of the PI3K-AKT and MAPK signaling pathways. Furthermore, the exogenous overexpression of ERBB3 partially reversed the inhibitory effects on EOC progression induced by NUF2 downregulation, while LY294002 and PD98059 partially reversed the effects of ERBB3 upregulation.ConclusionThese results showed that NUF2 promotes EOC progression through ERBB3-induced activation of the PI3K-AKT and MAPK signaling axes. These findings suggest that NUF2 might be a potential therapeutic target for EOC.

BackgroundKidney renal clear cell carcinoma (KIRC) is a malignant tumor with a high degree of immune infiltration. Identifying immune biomarkers is essential for the treatment of KIRC. Studies have identified the potential of NEIL3 to modulate the immune microenvironment and promote tumor progression. However, the role of NEIL3 in KIRC remains uncertain. This study was to investigate the effect of NEIL3 on the prognosis and immune infiltration of patients with KIRC.MethodsTCGA and GEO databases were used to study the expression of NEIL3 in KIRC. Cox regression analysis was used to examine the relationship between the expression of NEIL3 and clinicopathological variables and survival. Furthermore, Gene Set Cancer Analysis (GSCA) was applied to study the impact of NEIL3 methylation on outcomes of KIRC. Through gene ontology (GO) and Gene set enrichment (GSEA) analysis, the biological processes and signal pathways related to NEIL3 expression were identified. In addition, immune infiltration analysis was conducted via CIBERSORT analysis, ssGSEA analysis and TISIDB database.ResultsNEIL3 was overexpressed in KIRC, and it was significantly related with histologic grade, pathologic stage, T stage, M stage, and vital status of KIRC patients (P < 0.001). The expression of NEIL3 was associated with worse outcomes. Univariate and multivariate Cox analysis showed that NEIL3 may be an indicator of adverse outcomes in KIRC. GSEA analysis revealed that NEIL3 may be involved in signal pathways including cell cycle, DNA replication, mismatch repair, P53 signal pathway, and antigen processing and presentation. In addition, immune infiltration analysis showed a positive correlation between NEIL3 expression and multiple immune cells (activated CD8 T cells, activated dendritic cells, myeloid-derived suppressor cells, follicular helper T cells, and regulatory T cells) and immunoinhibitors (PD1, CTLA4, LAG3, TIGHT, IL10, and CD96).ConclusionNEIL3 is a potential independent biomarker of KIRC, which is relevant to immune infiltration.