N-trans-Feruloyloctopamine (FO), a natural compound, was reported in our previous study to inhibit a tumor cell malignant phenotype by AKT- and EMT-related signals and might be used as a promising drug for HCC treatment. However, the specific targets and detailed mechanisms still need to be clarified. Screening with RNA-Seq in Huh7 cells treated with FO revealed that 317 genes were modulated, of which 188 genes were upregulated and 129 genes were downregulated. Real-time cell analyzer and flow cytometry data reveal that tumor cell proliferation and apoptosis were impacted by FO. DAVID bioinformatic data showed that most of the biological process GO terms are related to proliferation and apoptosis. KEGG enrichment analysis showed that FO mainly regulates PI3K-AKT- and apoptosis-related signals, in which BBC3, DDIT3, NOXA, and CDKN1A on the surface serve as the novel targets of FO inducing HCC cell apoptosis. The result implied that FO might exacerbate HCC cell apoptosis by regulating BBC3, DDIT3, CDKN1A, and NOXA signals. The obstacle effect of FO can provide new targets and new credibility for the treatment of liver cancer.

中文翻译：

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N-trans-Feruloyloctopamine 唤醒 BBC3、DDIT3、CDKN1A 和 NOXA 信号以加速 HCC 细胞凋亡

N-反式-Feruloyloctopamine (FO) 是一种天然化合物，在我们之前的研究中被报道可通过 AKT 和 EMT 相关信号抑制肿瘤细胞恶性表型，并且可能用作治疗 HCC 的有前途的药物。但具体目标和详细机制仍有待明确。用 FO 处理的 Huh7 细胞中的 RNA-Seq 筛选显示 317 个基因受到调节，其中 188 个基因上调，129 个基因下调。实时细胞分析仪和流式细胞术数据显示肿瘤细胞增殖和凋亡受 FO 影响。DAVID 生物信息学数据显示，大部分生物过程 GO 术语都与增殖和凋亡有关。KEGG富集分析显示FO主要调节PI3K-AKT和凋亡相关信号，其中BBC3、DDIT3、NOXA、表面的 CDKN1A 和 CDKN1A 作为 FO 诱导 HCC 细胞凋亡的新靶点。结果暗示FO可能通过调节BBC3、DDIT3、CDKN1A和NOXA信号加剧HCC细胞凋亡。FO的障碍效应可以为肝癌的治疗提供新的靶点和新的可信度。