FNDC3B (fibronectin type III domain containing 3B) is highly expressed in hepatocellular carcinoma (HCC) and other cancer types, and fusion genes involving FNDC3B have been identified in HCC and leukemia. Growing evidence suggests the significance of FNDC3B in tumorigenesis, particularly in cell migration and tumor metastasis. However, its regulatory mechanisms remain elusive. In this study, we employed bioinformatic, gene regulation, and protein-DNA interaction screening to investigate the transcription factors (TFs) involved in regulating FNDC3B. Initially, 338 candidate TFs were selected based on previous chromatin immunoprecipitation (ChIP)-seq experiments available in public domain databases. Through TF knockdown screening and ChIP coupled with Droplet Digital PCR assays, we identified that E2F1 (E2F transcription factor 1) is crucial for the activation of FNDC3B. Overexpression or knockdown of E2F1 significantly impacts the expression of FNDC3B. In conclusion, our study elucidated the mechanistic link between FNDC3B and E2F1. These findings contribute to a better understanding of FNDC3B in tumorigenesis and provide insights into potential therapeutic targets for cancer treatment.

中文翻译：

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E2F1通过FNDC3B促进肝细胞癌细胞迁移

FNDC3B（含有 3B 的纤连蛋白 III 型结构域）在肝细胞癌 (HCC) 和其他癌症类型中高表达，并且已在 HCC 和白血病中鉴定出涉及 FNDC3B 的融合基因。越来越多的证据表明 FNDC3B 在肿瘤发生中的重要性，特别是在细胞迁移和肿瘤转移中。然而，其监管机制仍然难以捉摸。在本研究中，我们采用生物信息学、基因调控和蛋白质-DNA 相互作用筛选来研究参与调节 FNDC3B 的转录因子 (TF)。最初，根据公共领域数据库中现有的染色质免疫沉淀 (ChIP)-seq 实验，选择了 338 个候选 TF。通过 TF 敲除筛选和 ChIP 结合微滴式数字 PCR 检测，我们确定 E2F1（E2F 转录因子 1）对于 FNDC3B 的激活至关重要。 E2F1 的过表达或敲低显着影响 FNDC3B 的表达。总之，我们的研究阐明了 FNDC3B 和 E2F1 之间的机制联系。这些发现有助于更好地了解 FNDC3B 在肿瘤发生中的作用，并为癌症治疗的潜在治疗靶点提供见解。