Division of Digestive System, Department of Internal Medicine, The Second Affiliated Hospital, Shandong First Medical University, Tai'an, China.
Division of Digestive System, Department of Internal Medicine, The 960th Hospital of PLA, Tai'an, China.
Turk J Med Sci. 2023 Feb 28;53(5):1032-1044. doi: 10.55730/1300-0144.5668. eCollection 2023.
BACKGROUND/AIM: Hepatocellular carcinoma (HCC) ranks among the most prevalent malignancies worldwide and the third leading cause of cancer-related death. The TRIM (tripartite motif-containing) protein family members had been reported to be involved in carcinogenesis and tumor progression. Here we aimed to explore the expression profile of TRIM6 in HCC and investigate its clinical significance as well as underlying mechanisms.
We retrospectively enrolled 138 HCC patients that underwent surgical resection in our hospital and tested protein expression level of TRIM6 through immunohistochemical staining. The correlation between TRIM6 and patients' characteristics was assessed by Chi-square test. Log-rank test and Cox hazard regression test were conducted for univariate and multivariate survival analyses, respectively. Two human HCC cell lines, Huh7 and Hep3B, were subjected for knockdown and overexpression assays, followed by phonotype tests including proliferation and invasion. Nude mice were used to generate xenograft model to validate our findings in vivo.
TRIM6 was highly expressed in HCC specimen compared to nontumorous liver tissues. Higher TRIM6 expression was correlated with larger tumor size, later tumor stage, and worse prognosis. According to the cellular experiments, TRIM6-knockdown resulted in decreased expression of cyclin B1, c-Myc, Snail, MMP2, and VEGF-A. Consistently, TRIM6-knockdown led to impaired HCC proliferation, invasion, and angiogenesis. In contrast, TRIM6 overexpression showed opposite effects. Finally, the oncogenic role of TRIM6 in HCC was validated by in vivo mice experiments.
TRIM6 can serve as a novel prognostic factor for HCC, which functions by multiple signaling pathways.
背景/目的：肝细胞癌 (HCC) 是全球最常见的恶性肿瘤之一，也是癌症相关死亡的第三大主要原因。TRIM（三结构域含）蛋白家族成员已被报道参与癌症发生和肿瘤进展。在这里，我们旨在探讨 TRIM6 在 HCC 中的表达谱，并研究其临床意义及其潜在机制。
我们回顾性地招募了 138 名在我院接受手术切除的 HCC 患者，并通过免疫组织化学染色检测 TRIM6 的蛋白表达水平。通过卡方检验评估 TRIM6 与患者特征之间的相关性。对数秩检验和 Cox 风险回归检验分别用于单变量和多变量生存分析。我们对两种人 HCC 细胞系 Huh7 和 Hep3B 进行了敲低和过表达实验，随后进行了表型测试，包括增殖和侵袭。使用裸鼠生成异种移植模型，在体内验证我们的发现。
TRIM6 在 HCC 标本中的表达明显高于非肿瘤性肝组织。较高的 TRIM6 表达与肿瘤体积较大、肿瘤分期较晚和预后较差相关。根据细胞实验，TRIM6 敲低导致细胞周期蛋白 B1、c-Myc、Snail、MMP2 和 VEGF-A 的表达下调。一致地，TRIM6 敲低导致 HCC 增殖、侵袭和血管生成受损。相反，TRIM6 过表达显示出相反的效果。最后，通过体内小鼠实验验证了 TRIM6 在 HCC 中的致癌作用。
TRIM6 可以作为 HCC 的一种新的预后因素，通过多种信号通路发挥作用。
