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Meningioma-associated protein 30 accelerates the proliferation and invasion of hepatocellular carcinoma by modulating Wnt/GSK-3β/β-catenin signaling
Journal of Bioenergetics and Biomembranes ( IF 2.9 ) Pub Date : 2021-01-06 , DOI: 10.1007/s10863-020-09864-2
Yu Zhang 1 , Hui Li 1 , Jixin Wang 2 , Xilin Geng 1 , Jun Hai 1
Affiliation  

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.



中文翻译:

脑膜瘤相关蛋白30通过调节Wnt/GSK-3β/β-catenin信号促进肝细胞癌的增殖和侵袭

脑膜瘤相关蛋白 30 (MAC30) 最近被确定为一种新的肿瘤相关蛋白,与多种肿瘤类型有关。然而,尚未研究 MAC30 在肝细胞癌 (HCC) 中的作用。在目前的研究中,我们探索了 MAC30 在 HCC 中的表达、生物学功能和潜在机制。我们发现 MAC30 表达在 HCC 组织和细胞系中显着升高。功能性体外测定表明 MAC30 的敲低抑制了 HCC 细胞的增殖和侵袭,而 MAC30 过表达促进了这些生物学行为。此外,MAC30 的敲低降低了糖原合酶激酶 (GSK)-3β 磷酸化水平和 β-catenin 表达,导致 HCC 细胞中 Wnt/β-catenin 信号传导失活。GSK-3β 的抑制或重新激活 Wnt/β-catenin 信号显着逆转了 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,Wnt/β-catenin 信号传导的抑制消除了 MAC30 诱发的 HCC 细胞致癌作用。此外,MAC30 的敲低阻碍了肿瘤的形成和体内 HCC 细胞的生长速度。总之,我们的数据确认 MAC30 是 HCC 中潜在的肿瘤促进因子,它通过 Wnt/β-catenin 信号传导的上调加速了 HCC 的增殖和侵袭。我们的研究表明 MAC30 是 HCC 的潜在抗癌靶点。Wnt/β-catenin 信号的抑制消除了 MAC30 诱发的 HCC 细胞致癌作用。此外,MAC30 的敲低阻碍了肿瘤的形成和体内 HCC 细胞的生长速度。总之,我们的数据确认 MAC30 是 HCC 中潜在的肿瘤促进因子,它通过 Wnt/β-catenin 信号传导的上调加速了 HCC 的增殖和侵袭。我们的研究表明 MAC30 是 HCC 的潜在抗癌靶点。Wnt/β-catenin 信号的抑制消除了 MAC30 诱发的 HCC 细胞致癌作用。此外,MAC30 的敲低阻碍了肿瘤的形成和体内 HCC 细胞的生长速度。总之,我们的数据确认 MAC30 是 HCC 中潜在的肿瘤促进因子,它通过 Wnt/β-catenin 信号传导的上调加速了 HCC 的增殖和侵袭。我们的研究表明 MAC30 是 HCC 的潜在抗癌靶点。

更新日期:2021-01-06
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