背景:FAM110A属于FAM110家族,主要在与细胞周期相关的生物过程中起作用。然而,FAM110A参与的生物学功能在很大程度上是不明确的。特别是,它在癌症中的潜在作用仍然未知。本研讨的目标是揭开FAM110A在胰腺癌中的感化和机制。方法:基于生物信息学数据库,qPCR和蛋白质印迹分析,我们验证了FAM110A在PDAC中的表达水平升高。随后,FAM110A,HIST1H2BK和TSPAN1过表达或敲低稳定转染的细胞用于生物学功能研究,以探索体外和体内在PDAC中的作用。RNA-Seq,Westernblot和荧光素酶-报告基因测定用于探索FAM110A在PDAC中的作用机制。并通过肿瘤表型拯救实验验证了所涉及的通路。结果:在这项研究中,我们首次证明FAM110A是一种促进细胞增殖的癌基因,迁移,胰腺癌的侵袭和肿瘤发生。HIST1H2BK被确定为FAM110A的下游靶标,而HIST1H2BK敲低可以消除FAM110A过表达引起的促进作用。此外,第一次,我们揭示了HIST1H2BK在胰腺癌中的致癌作用,HIST1H2BK的促肿瘤能力可能与其对G9a的调节作用有关。此外,我们证明了TSPAN1对FAM110A表现出积极的转录调节作用。结论:总的来说,FAM110A在PDAC中起致癌作用,新发现的TSPAN1/FAM110A/HIST1H2BK/G9a通路参与胰腺癌进展的调节,为胰腺癌治疗提供了一种新的预后和治疗策略。
Background: FAM110A belongs to the FAM110 family, which mainly functions in biological processes associated with the cell cycle. However, the biological functions in which FAM110A participates are largely undefined. In particular, its potential role in cancer remains unknown. The goal of this study was to uncover the role and mechanism of FAM110A in pancreatic cancer. Methods: Based on bioinformatics databases, qPCR and Western blot assays, we verified the elevated expression level of FAM110A in PDAC. Subsequently, FAM110A,
HIST1H2BK and TSPAN1 overexpression or knockdown stable transfected cells were employed for biological functions\' studies to explore the role in PDAC in vitro and in vivo. RNA-Seq, Western blot and luciferase-reporter assays were used to explore mechanism of FAM110A action in PDAC, and the involved pathway was verified by tumor phenotypic rescue experiments. Results: In this study, we demonstrated for the first time that FAM110A is an oncogene that promotes cell proliferation, migration, invasion and tumorigenesis in pancreatic cancer.
HIST1H2BK was identified as the downstream target of FAM110A, while the promotion effect caused by FAM110A overexpression could be abolished by
HIST1H2BK knockdown. Moreover, for the first time, we revealed the oncogenic role of
HIST1H2BK in pancreatic cancer, and the tumor-promoting capacity of
HIST1H2BK may be associated with its regulatory effect on G9a. In addition, we demonstrated that TSPAN1 displayed a positive transcriptional regulatory effect on FAM110A. Conclusions: Collectively, FAM110A plays an oncogenic role in PDAC, and the newly identified TSPAN1/FAM110A/HIST1H2BK/G9a pathway is involved in the modulation of pancreatic cancer progression and provides a novel prognostic and therapeutic strategy for pancreatic cancer treatment.