Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
FEBS Open Bio. 2024 Apr;14(4):687-694. doi: 10.1002/2211-5463.13783. Epub 2024 Feb 25.
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.
FNDC3B（含 III 型纤连蛋白结构域的 FNDC3B）在肝癌（HCC）和其他癌症类型中高度表达，并且已经在 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，其调节机制仍不清楚。在这项研究中，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调节 FNDC3B 的转录因子（TFs）。最初，根据公共领域数据库中先前的染色质免疫沉淀（ChIP）-seq 实验，选择了 338 个候选 TFs。通过 TF 敲低筛选和 ChIP 与液滴数字 PCR 测定相结合，我们鉴定出 E2F1（E2F 转录因子 1）对于 FNDC3B 的激活至关重要。E2F1 的过表达或敲低显著影响 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理解 FNDC3B 在肿瘤发生中的作用，并为癌症治疗提供潜在的治疗靶点的见解。
