Department of Interventional Radiology, Zhongshan Hospital, Fudan University, China.
MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Biochem Biophys Res Commun. 2019 Jun 11;513(4):834-840. doi: 10.1016/j.bbrc.2019.04.081. Epub 2019 Apr 16.
Hepatocellular carcinoma (HCC) presents a great burden for patients worldwide, and metastasis of HCC remains problematic. Arsenic trioxide is a traditional drug that has shown excellent efficacy when applied as cancer therapy. Our study explored the antimetastatic mechanism of arsenic trioxide in HCC. We investigated changes in pyruvate kinase muscle isoform 2 (PKM2) and maternal expression gene 3 (MEG3) following treatment with arsenic trioxide in HCC cells. Consequently, arsenic trioxide negatively regulated PKM2 and positively regulated MEG3. We explored migration ability and the expression of the epithelial to mesenchymal transition (EMT)-related biomarkers E-cadherin, N-cadherin and Vimentin by silencing MEG3 under arsenic trioxide treatment. The wound healing assay showed that arsenic trioxide inhibited the migration of HCC, but silencing MEG3 partially reversed this effect. On the other hand, the EMT-related biomarkers are alleviated under the treatment of arsenic trioxide, but this effect deteriorated when MEG3 is silenced. In conclusion, our study demonstrates a novel mechanism by which arsenic trioxide inhibits EMT in hepatocellular carcinoma by promoting lncRNA MEG3 and PKM2 negatively regulating MEG3.
肝细胞癌 (HCC) 给全球患者带来了巨大的负担，而 HCC 的转移仍然是一个问题。三氧化二砷是一种传统药物，在癌症治疗中已显示出优异的疗效。我们的研究探讨了三氧化二砷在 HCC 中的抗转移机制。我们研究了 HCC 细胞用三氧化二砷处理后丙酮酸激酶肌肉同工型 2 (PKM2) 和母系表达基因 3 (MEG3) 的变化。结果表明，三氧化二砷负调控 PKM2，正调控 MEG3。我们通过在三氧化二砷处理下沉默 MEG3 来探索迁移能力和上皮-间充质转化 (EMT) 相关生物标志物 E-钙粘蛋白、N-钙粘蛋白和波形蛋白的表达。划痕愈合实验表明，三氧化二砷抑制 HCC 的迁移，但沉默 MEG3 部分逆转了这种作用。另一方面，EMT 相关生物标志物在三氧化二砷处理下得到缓解，但当沉默 MEG3 时，这种作用恶化。总之，我们的研究表明，三氧化二砷通过促进 lncRNA MEG3 和 PKM2 负调控 MEG3 来抑制 EMT 的新机制。
