Salt-inducible kinase 2 (SIK2) has been reported to be involved in cancer progression in a dichotomous manner. However, the role and mechanism of action of SIK2 in hepatocellular carcinoma (HCC) progression remain elusive. SIK2 expression in HCC tissues in The Cancer Genome Atlas (TCGA) database was analyzed using the AIPuFu platform. SIK2 expression in HCC cells was examined by quantitative real-time PCR and western blot analysis. The expression of N-cadherin, E-cadherin, β-catenin, and c-Myc was detected by western blot analysis. SIK2 was downregulated in HCC tissues compared with normal patients, and low SIK2 expression was correlated with poor prognosis in HCC patients in TCGA database. SIK2 was lowly expressed in HCC cells than that in normal human liver epithelial cells. SIK2 overexpression inhibited cell proliferation and invasion and promoted apoptosis in HCC cells, while SIK2 silencing exerted the opposite effects. Additionally, SIK2 overexpression inactivated the Wnt/β-catenin pathway in HCC cells, as evidenced by the reduced expression of β-catenin and c-Myc. β-catenin overexpression rescued the inhibitory effects of SIK2 on the malignant properties of HCC cells. Xenograft tumor experiment confirmed that SIK2 suppressed the growth of HCC cells in vivo. In conclusion, SIK2 exerted anti-tumor activity in HCC via inactivating the Wnt/β-catenin signaling pathway.

中文翻译：

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盐诱导激酶 2 在肝细胞癌中起肿瘤抑制作用

据报道，盐诱导激酶 2 (SIK2) 以二分法参与癌症进展。然而，SIK2 在肝细胞癌 (HCC) 进展中的作用和作用机制仍然难以捉摸。使用 AIPuFu 平台分析癌症基因组图谱 (TCGA) 数据库中 HCC 组织中的 SIK2 表达。通过定量实时PCR和蛋白质印迹分析检查HCC细胞中的SIK2表达。通过蛋白质印迹分析检测N-钙粘蛋白、E-钙粘蛋白、β-连环蛋白和c-Myc的表达。与正常患者相比，HCC 组织中的 SIK2 表达下调，在 TCGA 数据库中，SIK2 的低表达与 HCC 患者的不良预后相关。SIK2在HCC细胞中的表达低于在正常人肝上皮细胞中的表达。SIK2 过表达抑制细胞增殖和侵袭并促进 HCC 细胞凋亡，而 SIK2 沉默则发挥相反的作用。此外，SIK2 过表达使 HCC 细胞中的 Wnt/β-catenin 通路失活，β-catenin 和 c-Myc 的表达降低就证明了这一点。β-连环蛋白过表达挽救了 SIK2 对 HCC 细胞恶性特性的抑制作用。异种移植肿瘤实验证实SIK2抑制体内HCC细胞的生长。总之，SIK2 通过灭活 Wnt/β-catenin 信号通路在 HCC 中发挥抗肿瘤活性。β-连环蛋白过表达挽救了 SIK2 对 HCC 细胞恶性特性的抑制作用。异种移植肿瘤实验证实SIK2抑制体内HCC细胞的生长。总之，SIK2 通过灭活 Wnt/β-catenin 信号通路在 HCC 中发挥抗肿瘤活性。β-连环蛋白过表达挽救了 SIK2 对 HCC 细胞恶性特性的抑制作用。异种移植肿瘤实验证实SIK2抑制体内HCC细胞的生长。总之，SIK2 通过灭活 Wnt/β-catenin 信号通路在 HCC 中发挥抗肿瘤活性。