SAC3D1 在肝细胞癌中激活 Wnt/β-catenin 信号通路。
SAC3D1 activates Wnt/β‑catenin signalling in hepatocellular carcinoma.
机构信息
Laboratory Center of Bozhou People's Hospital, The Bozhou Hospital Affiliated to Anhui Medical University, Bozhou, Anhui 236800, P.R. China.
出版信息
Mol Med Rep. 2022 Oct;26(4). doi: 10.3892/mmr.2022.12833. Epub 2022 Aug 25.
β‑catenin accumulates in hepatocellular carcinoma (HCC); therefore, understanding the mechanism of Wnt/β‑catenin pathway activation is important for HCC therapy. SAC3 domain containing 1 (SAC3D1) is involved in numerous types of cancer, such as gastric cancer. To the best of our knowledge, however, the role of SAC3D1 in HCC has not yet been elucidated. Here, the expression of SAC3D in HCC was examined by quantitative PCR, western blotting and immunohistochemistry. The function of SAC3D1 in HCC were examined using Cell Counting Kit‑8 and anchorage‑independent growth assay. It was found that the levels of SAC3D1 mRNA and protein were upregulated in HCC. When SAC3D1 was overexpressed, the proliferation of HCC cells was promoted; when the expression of SAC3D1 was disrupted, HCC cell growth was inhibited. When the molecular mechanism was investigated using immunoprecipitation, it was found that SAC3D1 interacted with axin, inhibiting ubiquitination of β‑catenin and elevating protein levels of β‑catenin. In summary, the present study revealed the promoting function of SAC3D1 in the progression of HCC. SAC3D1 may be a promising target for HCC therapy.
β-连环蛋白在肝细胞癌(HCC)中积累;因此,了解 Wnt/β-连环蛋白通路激活的机制对于 HCC 治疗很重要。SAC3 结构域包含 1(SAC3D1)参与多种类型的癌症,例如胃癌。然而,据我们所知,SAC3D1 在 HCC 中的作用尚未阐明。在这里,通过定量 PCR、western blot 和免疫组织化学检查了 SAC3D 在 HCC 中的表达。使用细胞计数试剂盒-8 和非锚定依赖性生长测定检查了 SAC3D1 在 HCC 中的功能。结果发现 SAC3D1 mRNA 和蛋白水平在 HCC 中上调。当 SAC3D1 过表达时,促进了 HCC 细胞的增殖;当 SAC3D1 的表达被破坏时,抑制了 HCC 细胞的生长。当使用免疫沉淀研究分子机制时,发现 SAC3D1 与轴蛋白相互作用,抑制 β-连环蛋白的泛素化并提高 β-连环蛋白的蛋白水平。综上所述,本研究揭示了 SAC3D1 在 HCC 进展中的促进作用。SAC3D1 可能是 HCC 治疗的有前途的靶点。