Gallic Acid Suppressed Tumorigenesis by an LncRNA MALAT1-Wnt/β-Catenin Axis in Hepatocellular Carcinoma.
Gallic Acid Suppressed Tumorigenesis by an LncRNA MALAT1-Wnt/β-Catenin Axis in Hepatocellular Carcinoma.
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没食子酸通过 LncRNA MALAT1-Wnt/β-Catenin 轴抑制肝细胞癌的肿瘤发生
DOI：
10.3389/fphar.2021.708967
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发表时间：
2021
影响因子：
5.6
通讯作者：
Fu WM
中科院分区：
文献类型：
--
作者：
Shi CJ;Zheng YB;Pan FF;Zhang FW;Zhuang P;Fu WM
没食子酸（3,4,5-三羟基苯甲酸；GA）是一种天然酚酸，在许多天然产物中含量丰富。越来越多的证据表明，GA在多种癌症中具有抗癌作用。然而，其对肝细胞癌（HCC）的抗肿瘤作用及其机制尚不清楚。在本研究中，我们发现GA抑制了肝癌细胞的体外活力和转移，抑制了肝癌细胞的体内肿瘤生长。结果表明，GA抑制了β-catenin的表达，导致Wnt/β-catenin信号通路的功能失活。长链非编码RNA分子（long noncoding RNA molecules, lncRNAs）作为一类重要的调控分子，因其在多种生物过程和人类疾病中的重要作用而受到广泛关注。为了进一步确定哪些lncRNA参与了ga介导的这一过程，我们选择了几个与Wnt/β-catenin信号传导相关的lncRNA来检测它们在ga处理的HCC细胞中的表达谱。其中，转移相关肺腺癌转录本1 （MALAT1）是最有希望的候选基因。此外，GA显著下调了MALAT1。其过表达部分逆转了ga诱导的对细胞增殖和转移的抑制作用；成功地消除了GA对Wnt/β-catenin信号传导的抑制作用。综上所述，我们的研究结果表明，GA在体外和体内通过MALAT1-Wnt/β-catenin信号轴抑制肿瘤的发生，表明GA作为HCC患者的化疗预防和化疗药物具有很大的潜力。
Gallic acid (3,4,5-trihydroxybenzoic acid; GA), a natural phenolic acid, is abundantly found in numerous natural products. Increasing evidence have demonstrated that GA plays anti-cancer roles in multiple cancers. However, its anti-tumor effects on hepatocellular carcinoma (HCC) and the underlying mechanism remain obscure. In the present study, we found that GA suppressed the in vitro cell viability and metastasis and inhibited the in vivo tumor growth of HCC cells. The underlying mechanism was further to investigate and it was showed that GA suppressed the expression of β-catenin and led to the functional inactivation of Wnt/β-catenin signaling. As a kind of significant regulators, the long noncoding RNA molecules (lncRNAs) have attracted widespread attentions for their critical roles in diverse biological process and human diseases. To further identify which lncRNA participated this GA-mediated process, several lncRNAs related to Wnt/β-catenin signaling were chosen for examination of their expression profiling in the GA-treated HCC cells. Of which, Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) was the most promising candidate. And moreover, MALAT1 was significantly down-regulated by GA. Its overexpression partially reversed the GA-induced the inhibitory effects on cell proliferation and metastasis; and successfully abolished the suppressive effect of GA on Wnt/β-catenin signaling. In conclusion, our results indicated that GA suppressed tumorigenesis in vitro and in vivo by the MALAT1-Wnt/β-catenin signaling axis, suggesting that GA has great potential to be developed as a chemo-prevention and chemotherapy agent for HCC patients.
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