Chen Zhaobin, Huang Liyuan, Ding Leping, Zhang Congrui, Li Yanpeng, Wang Bingyuan, Shi Junping, Zhang Jing
School of Clinical Medicine, Jining Medical University, Jining, Shandong, China.
Medical Research Center, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
Sci Rep. 2025 Jul 10;15(1):24824. doi: 10.1038/s41598-025-07585-3.
The Nuclear Factor of Activated T-cells cytoplasmic 1 (NFATc1) is identified to be an oncogene in several human cancers. However, its specific role in HCC progression and the relevant mechanisms remain unclear. To investigate this, we analyzed NFATc1 expression in clinical HCC samples (n = 289) using RT-qPCR, Western blotting, and immunohistochemistry (IHC). In vitro assays assessed HCC cell proliferation, migration, invasion, apoptosis, and cell cycle, while in vivo studies using BALB/c nude mice evaluated the effects of NFATc1 on HCC growth and metastasis. Mechanistic studies were conducted to explore NFATc1's downstream signaling pathways. Results revealed that NFATc1 is significantly upregulated in HCC tissues compared to adjacent non-cancerous tissues, correlating with poor prognosis. Overexpression of NFATc1 enhanced HCC cell proliferation, migration, and invasion both in vitro and in vivo, while silencing NFATc1 reduced these malignant traits. Mechanistic analysis indicated that NFATc1 activation correlates with NF-κB/TMP21 signaling and senescence-associated secretory phenotype (SASP) amplification, independent of growth arrest. These findings suggest that NFATc1 plays a pivotal role in HCC progression, potentially through the modulation of SASP activation. Targeting NFATc1 and its signaling pathways could be a promising therapeutic approach for HCC.
活化T细胞核因子细胞质1（NFATc1）被确定为几种人类癌症中的一种癌基因。然而，其在肝癌进展中的具体作用及相关机制仍不清楚。为了研究这一点，我们使用逆转录定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹法和免疫组织化学（IHC）分析了289例临床肝癌样本中NFATc1的表达。体外实验评估了肝癌细胞的增殖、迁移、侵袭、凋亡和细胞周期，而使用BALB/c裸鼠的体内研究评估了NFATc1对肝癌生长和转移的影响。进行了机制研究以探索NFATc1的下游信号通路。结果显示，与相邻的非癌组织相比，NFATc1在肝癌组织中显著上调，与预后不良相关。NFATc1的过表达在体外和体内均增强了肝癌细胞的增殖、迁移和侵袭，而沉默NFATc1则降低了这些恶性特征。机制分析表明，NFATc1的激活与核因子κB/TMP21信号传导和衰老相关分泌表型（SASP）放大相关，与生长停滞无关。这些发现表明，NFATc1可能通过调节SASP激活在肝癌进展中起关键作用。靶向NFATc1及其信号通路可能是一种有前景的肝癌治疗方法。
