Tong Qing, Yi Mingyu, Kong Panpan, Xu Lin, Huang Wukui, Niu Yue, Gan Xiaojing, Zhan Huan, Tian Rui, Yan Dong
Department of Hepatopancreatobiliary Surgery, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China.
The Third Affiliated, Teaching Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Cancer Cell Int. 2022 Sep 6;22(1):278. doi: 10.1186/s12935-022-02692-x.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has an extremely poor prognosis. We aimed to determine the latent relationships between TRIM36 regulation of apoptosis and the Wnt/β-catenin pathway in HCC.
Immunohistochemistry and western blotting were used to characterize the aberrant expression of TRIM36 in HCC and adjacent tissues. Clinical information was analyzed using Kaplan-Meier and Cox methods. RNA-seq of potential targets was conducted to detect the regulation of TRIM36. Apoptosis assays and cellular proliferation, invasion and migration were conducted in a loss- and gain-of-function manner in cultured cells to determine the biological functions of TRIM36. A rescue experiment was conducted to confirm the role of Wnt/β-catenin signaling in TRIM36 regulation. Finally, in vivo experiments were conducted using cell line-derived xenografts in nude mice to validate the central role of TRIM36 in HCC.
TRIM36 expression was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues. TRIM36 repressed the proliferation, migration, and invasion of Huh7 and HCCLM3 cells, whereas it stimulated apoptosis. Wnt/β-catenin signaling was inhibited by TRIM36, and rescue experiments highlighted its importance in HCC proliferation, migration, and invasion. In vivo experiments further confirmed the effects of sh-TRIM36 on HCC tumorigenesis, inhibition of apoptosis, and promotion of Wnt/β-catenin signaling.
Our study is the first to indicate that TRIM36 acts as a tumor suppressor in HCC. TRIM36 activates apoptosis and inhibits cellular proliferation, invasion, and migration via the Wnt/β-catenin pathway, which may serve as an important biomarker and promising therapeutic target for HCC.
肝细胞癌（HCC）是原发性肝癌最常见的类型，预后极差。我们旨在确定TRIM36调控细胞凋亡与HCC中Wnt/β-连环蛋白信号通路之间的潜在关系。
采用免疫组织化学和蛋白质印迹法来表征TRIM36在HCC及癌旁组织中的异常表达。使用Kaplan-Meier法和Cox法分析临床信息。对潜在靶点进行RNA测序以检测TRIM36的调控作用。在培养细胞中以功能缺失和功能获得的方式进行细胞凋亡检测以及细胞增殖、侵袭和迁移实验，以确定TRIM36的生物学功能。进行拯救实验以证实Wnt/β-连环蛋白信号在TRIM36调控中的作用。最后，在裸鼠中使用细胞系来源的异种移植进行体内实验，以验证TRIM36在HCC中的核心作用。
与相邻的非肿瘤组织相比，HCC组织中TRIM36表达明显下调。TRIM36抑制Huh7和HCCLM3细胞的增殖、迁移和侵袭，同时促进细胞凋亡。TRIM36抑制Wnt/β-连环蛋白信号，拯救实验突出了其在HCC增殖、迁移和侵袭中的重要性。体内实验进一步证实了sh-TRIM36对HCC肿瘤发生、细胞凋亡抑制及Wnt/β-连环蛋白信号促进的作用。
我们的研究首次表明TRIM36在HCC中作为肿瘤抑制因子发挥作用。TRIM36通过Wnt/β-连环蛋白信号通路激活细胞凋亡并抑制细胞增殖、侵袭和迁移，这可能作为HCC的重要生物标志物和有前景的治疗靶点。
