Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Pancreatology. 2024 Nov;24(7):1073-1083. doi: 10.1016/j.pan.2024.08.008. Epub 2024 Aug 13.
Helix-loop-helix transcription factor 4 (HTF4) as an anti-cancer target has been reported in many human cancers, but limited data exists regarding the effect of HTF4 in pancreatic cancer. In this study, we aimed to investigate the role of HTF4 in pancreatic cancer.
The expression levels of HTF4 in clinical pancreatic cancer samples were measured. HTF4 was knocked down or overexpressed in pancreatic cancer cells and was subsequently tested for bio-function using in vitro assays and in vivo. The regulation of HTF4 on GID2 was assessed via bioinformatic tools and dual-luciferase reporter assay.
We found that HTF4 was highly expressed in pancreatic cancer tissues and correlated with poor patient prognosis. In addition, knocking down HTF4 expression inhibited cell proliferation, migration, and invasion, whereas HTF4 overexpression exerted the opposite effect. Moreover, HTF4 promoted tumor growth and metastasis in pancreatic cancer. Further, HTF4 bound to the GID2 promoter region and promoted transcriptional activation of GID2 in pancreatic cancer cells. GID2 knockdown suppressed HTF4-induced malignant behaviors of pancreatic cancer cells.
Our findings suggest that the HTF4/GID2 axis accelerates the progression of pancreatic cancer, providing a potential therapeutic target and prognostic indicator for the treatment of pancreatic cancer patients.
螺旋-环-螺旋转录因子 4（HTF4）作为一种抗癌靶点已在许多人类癌症中得到报道，但关于 HTF4 在胰腺癌中的作用的数据有限。在这项研究中，我们旨在研究 HTF4 在胰腺癌中的作用。
测量了临床胰腺癌样本中 HTF4 的表达水平。在胰腺癌细胞中敲低或过表达 HTF4，并通过体外和体内实验检测其生物功能。通过生物信息学工具和双荧光素酶报告基因检测评估 HTF4 对 GID2 的调控作用。
我们发现 HTF4 在胰腺癌组织中高表达，并与患者预后不良相关。此外，敲低 HTF4 表达抑制细胞增殖、迁移和侵袭，而过表达 HTF4 则产生相反的效果。此外，HTF4 促进了胰腺癌的肿瘤生长和转移。进一步研究发现，HTF4 结合在 GID2 启动子区域，并促进了胰腺癌细胞中 GID2 的转录激活。GID2 敲低抑制了 HTF4 诱导的胰腺癌细胞恶性行为。
我们的研究结果表明，HTF4/GID2 轴加速了胰腺癌的进展，为治疗胰腺癌患者提供了一个潜在的治疗靶点和预后指标。
