Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Department of Oncology and Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China.
DNA Cell Biol. 2022 Jul;41(7):671-682. doi: 10.1089/dna.2022.0169. Epub 2022 May 30.
Forkhead box M1 (FOXM1) is a proliferative transcription factor and plays a vital role in many cancers. However, the function and molecular mechanism of FOXM1 in esophageal squamous cell carcinoma (ESCC) remain poorly understood. Hence, we aim to clarify the molecular basis of FOXM1-mediated ESCC progression. In this study, bioinformatics analysis showed that FOXM1 was mainly involved in key signal pathways, including cell proliferation, cell cycle, and homologous recombination in ESCC, and predicted that CDC6 might be a potential regulatory target gene of FOXM1. The results revealed that FOXM1 and CDC6 were significantly overexpressed in ESCC tissue and cell line, and their expression was positively correlated. Further studies showed that FOXM1 directly transcriptionally activated CDC6 by binding to its promoter region in ESCC cells. Moreover, FOXM1 mediated ESCC cell proliferation by regulating CDC6 expression, which may be related to promoting G1-S phase transition of cell cycle. Taken together, FOXM1-CDC6 axis mediates ESCC malignant proliferation and may serve as a potential biological target for ESCC treatment.
叉头框转录因子 M1（FOXM1）是一种增殖转录因子，在许多癌症中发挥着重要作用。然而，FOXM1 在食管鳞状细胞癌（ESCC）中的功能和分子机制仍知之甚少。因此，我们旨在阐明 FOXM1 介导的 ESCC 进展的分子基础。在这项研究中，生物信息学分析表明，FOXM1 主要参与 ESCC 中的关键信号通路，包括细胞增殖、细胞周期和同源重组，并且预测 CDC6 可能是 FOXM1 的潜在调节靶基因。结果表明，FOXM1 和 CDC6 在 ESCC 组织和细胞系中均显著过表达，且其表达呈正相关。进一步的研究表明，FOXM1 通过结合 ESCC 细胞中其启动子区域，直接转录激活 CDC6。此外，FOXM1 通过调节 CDC6 表达来介导 ESCC 细胞增殖，这可能与促进细胞周期的 G1-S 期转变有关。总之，FOXM1-CDC6 轴介导 ESCC 恶性增殖，可能成为 ESCC 治疗的潜在生物学靶点。
