Zhang Yu, Li Hui, Wang Jixin, Geng Xilin, Hai Jun
Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Xi'an, 710068, China.
General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710068, China.
J Bioenerg Biomembr. 2021 Feb;53(1):73-83. doi: 10.1007/s10863-020-09864-2. Epub 2021 Jan 6.
Meningioma-associated protein 30 (MAC30) has been recently identified as a new tumor-associated protein that is implicated in multiple tumor types. However, the role of MAC30 in hepatocellular carcinoma (HCC) has not been studied. In the current study, we explored the expression, biological function and underlying mechanism of MAC30 in HCC. We found that MAC30 expression was significantly elevated in HCC tissues and cell lines. Functional in vitro assays demonstrated that the knockdown of MAC30 inhibited the proliferation and invasion of HCC cells, while MAC30 overexpression facilitated these biological behaviors. Moreover, the knockdown of MAC30 decreased glycogen synthase kinase (GSK)-3β phosphorylation level and β-catenin expression, leading to the inactivation of Wnt/β-catenin signaling in HCC cells. The inhibition of GSK-3β or reactivation Wnt/β-catenin signaling markedly reversed MAC30 knockdown-mediated inhibitory effects on the proliferation and invasion of HCC cells. Notably, the inhibition of Wnt/β-catenin signaling abrogated the MAC30-evoked oncogenic role in HCC cells. In addition, the knockdown of MAC30 impeded tumor formation and the growth rate of HCC cells in vivo. Taken together, our data recognized MAC30 as a potential tumor-promotion factor in HCC, which accelerated the proliferation and invasion of HCC through the up-regulation of Wnt/β-catenin signaling. Our study suggests MAC30 as a potential anticancer target for HCC.
脑膜瘤相关蛋白30（MAC30）最近被鉴定为一种新的肿瘤相关蛋白，与多种肿瘤类型有关。然而，MAC30在肝细胞癌（HCC）中的作用尚未得到研究。在本研究中，我们探讨了MAC30在HCC中的表达、生物学功能及潜在机制。我们发现MAC30在HCC组织和细胞系中的表达显著升高。体外功能试验表明，敲低MAC30可抑制HCC细胞的增殖和侵袭，而MAC30过表达则促进这些生物学行为。此外，敲低MAC30可降低糖原合酶激酶（GSK）-3β的磷酸化水平和β-连环蛋白的表达，导致HCC细胞中Wnt/β-连环蛋白信号失活。抑制GSK-3β或重新激活Wnt/β-连环蛋白信号可显著逆转MAC30敲低介导的对HCC细胞增殖和侵袭的抑制作用。值得注意的是，抑制Wnt/β-连环蛋白信号可消除MAC30在HCC细胞中引发的致癌作用。此外，敲低MAC30可阻碍体内HCC细胞的肿瘤形成和生长速度。综上所述，我们的数据表明MAC30是HCC中一种潜在的肿瘤促进因子，它通过上调Wnt/β-连环蛋白信号加速HCC的增殖和侵袭。我们的研究提示MAC30作为HCC潜在的抗癌靶点。
