胰腺癌（PC）是最致命的恶性肿瘤之一。据报道，NOB1 同源物 (PNO1) 的伴侣参与肿瘤发生。然而，PNO1 在 PC 中的作用仍有待阐明。本研究的目的是探讨 PNO1 对 PC 进展的影响以及与 E2F 转录因子 1 (E2F1) 相关的可能机制，E2F1 是 JASPAR 数据库预测的一种转录因子，可与 PNO1 启动子区域结合并促进增殖。胰腺导管腺癌。首先，通过基因表达谱交互分析数据库分析PC组织中PNO1的表达及其与生存率的关系。使用蛋白质印迹和逆转录定量聚合酶链反应来评估几种 PC 细胞系中的 PNO1 表达。 PNO1 沉默后，通过集落形成测定、5-乙炔基-2'-脱氧尿苷染色、伤口愈合和 Transwell 测定来测量细胞增殖、迁移和侵袭。然后，使用C11-BODIPY581/591探针估算PANC-1细胞中的脂质活性氧。测量了谷胱甘肽、丙二醛和铁的水平。 PNO1 和 E2F1 之间的结合通过荧光素酶和染色质免疫沉淀 (ChIP) 测定得到证实。随后，E2F1 在 PNO1 敲低的 PANC-1 细胞中过表达，以进行救援实验。结果显示，PNO1在PC组织中高表达，且PNO1表达与总生存率和无病生存率呈正相关。 PC 细胞系中也观察到 PNO1 表达显着升高。 PNO1 敲除抑制 PANC-1 细胞的增殖、迁移和侵袭。此外，PNO1 沉默的 PANC-1 细胞中铁死亡得到促进。荧光素酶和 ChIP 检测结果表明 E2F1 可以结合 PNO1 启动子区域。拯救实验表明，E2F1 过表达逆转了 PNO1 耗竭对 PANC-1 细胞恶性行为和铁死亡的影响。综上所述，E2F1转录激活的PNO1促进PC的恶性进展并抑制PC的​​铁死亡。

Pancreatic cancer (PC) is one of the deadliest malignancies. Partner of NOB1 homolog (PNO1) has been reported to be involved in tumorigenesis. However, the role of PNO1 in PC remains to be elucidated. The purpose of this study was to examine the effects of PNO1 on the progression of PC and the possible mechanism related to E2F transcription factor 1 (E2F1), a transcription factor predicted by the JASPAR database to bind to the PNO1 promoter region and promoted the proliferation of pancreatic ductal adenocarcinoma. First, PNO1 expression in PC tissues and its association with survival rate were analyzed by the Gene Expression Profiling Interactive Analysis database. Western blot and reverse transcription-quantitative polymerase chain reaction were used to evaluate PNO1 expression in several PC cell lines. After PNO1 silencing, cell proliferation, migration, and invasion were measured by colony formation assay, 5-ethynyl-2'-deoxyuridine staining, wound healing, and transwell assays. Then, the lipid reactive oxygen species in PANC-1 cells was estimated by using C11-BODIPY581/591 probe. The levels of glutathione, malondialdehyde, and iron were measured. The binding between PNO1 and E2F1 was confirmed by luciferase and chromatin immunoprecipitation (ChIP) assays. Subsequently, E2F1 was overexpressed in PANC-1 cells with PNO1 knockdown to perform the rescue experiments. Results revealed that PNO1 was highly expressed in PC tissues and PNO1 expression was positively correlated with overall survival rate and disease-free survival rate. Significantly elevated PNO1 expression was also observed in PC cell lines. PNO1 knockdown inhibited the proliferation, migration, and invasion of PANC-1 cells. Moreover, ferroptosis was promoted in PNO1-silenced PANC-1 cells. Results of luciferase and ChIP assays indicated that E2F1 could bind to PNO1 promoter region. Rescue experiments suggested that E2F1 overexpression reversed the impacts of PNO1 depletion on the malignant behaviors and ferroptosis in PANC-1 cells. Summing up, PNO1 transcriptionally activated by E2F1 promotes the malignant progression and inhibits the ferroptosis of PC.