Oleanolic acid inhibits the migration and invasion of hepatocellular carcinoma cells by promoting microRNA-122 expression
Oleanolic acid inhibits the migration and invasion of hepatocellular carcinoma cells by promoting microRNA-122 expression
复制标题
DOI：
10.1691/ph.2021.1366
复制
发表时间：
2021-09-01
期刊：
影响因子：
1.6
通讯作者：
Liu, Deming
中科院分区：
文献类型：
--
作者：
He, Yujiao;Liu, Xiao;Liu, Deming
microRNA作为重要的内源性基因功能调节因子在肿瘤的发生发展中起着重要作用。它们也被认为是癌症诊断和预后的可靠生物标志物。肝细胞癌（Hepatocellular carcinoma，HCC）是一种常见而复杂的恶性肿瘤，在世界范围内具有较高的发病率和死亡率。microRNA-122（miR-122）是一种肝脏特异性microRNA，与肝癌转移密切相关，是一个很有前途的药物设计和开发靶点。在这项研究中，我们进行了一个基于细胞的筛选方法来发现miR-122激活剂，并发现油酸（OA），一种天然的五环三萜，以浓度依赖性的方式特异性增加miR-122的表达。采用两种肝癌细胞系（HepG 2和Sk-hep-1细胞）来评价OA对细胞迁移和侵袭能力的影响。结果表明，OA通过上调miR-122的表达，减弱了肝癌细胞的迁移和侵袭能力。另外，OA还可增加E-cadherin的表达，降低beta-catenin、N-cadherin和vimentin的表达。在用miR-122抑制剂敲低miR-122后，我们发现OA对这些上皮间质转化（EMT）相关分子的影响明显减弱，表明OA通过增加miR-122的表达而发挥抗EMT作用。这些发现有助于更好地理解O angstrom抗转移活性的分子机制。
MicroRNAs are emerging as important endogenous regulators of gene function and they are playing an important role in the occurrence and development of cancer. They are also regarded as robust biomarkers of cancer diagnosis and prognosis. Hepatocellular carcinoma (HCC) is a common and complex human malignancy with high mortality and morbidity in the world. MicroRNA-122 (miR-122) is a liver-specific microRNA and is closely associated with HCC metastasis, which makes miR-122 a promising target for drug design and development. In this study, we performed a cell-based screening method for discovering miR-122 activators and found that oleanolic acid (OA), a natural pentacyclic triterpene, specifically increased miR-122 expression in a concentration-dependent manner. Two HCC cell lines (HepG2 and Sk-hep-1 cells) were used to evaluate the effect of OA on cell migration and invasion abilities. The results indicated that OA attenuated the migration and invasion abilities of HCC cells by upregulating miR-122 expression. In addition, OA increased the expression of E-cadherin and decreased the expression of beta-catenin, N-cadherin and vimentin. After knocking down miR-122 with miR-122 inhibitor, we found that the effect of OA on these epithelial-to-mesenchymal transition (EMT) related molecules was significantly weakened, indicating OA exhibited anti-EMT effect by increasing the expression of miR-122. These finding may help to better understand the molecular mechanism of O angstrom s anti-metastasis activity.