Zhang Tong, Liu Wei, Meng Wei, Zhao Hui, Yang Qing, Gu Shi-Jie, Xiao Cui-Cui, Jia Chang-Chang, Fu Bin-Sheng
Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
Organ Transplantation Institute of Sun Yat-sen University, Guangzhou, People's Republic of China.
Onco Targets Ther. 2018 Apr 5;11:1929-1939. doi: 10.2147/OTT.S154416. eCollection 2018.
Hepatocellular carcinoma (HCC) accounts for more than 90% of primary liver cancer. Although great progress has been made on HCC molecular mechanism and therapy techniques, the prognosis of HCC patient is poor due to high metastasis and recurrence.
Expression of miR-542-3p was quantified by quantitative real-time PCR (qRT-PCR). The role of miR-542-3p in HCC metastasis was examined using transwell and 3D-culture assay. qRT-PCR, Western blotting and luciferase reporter assay were used to elucidate the mechanisms of miR-542-3p-mediated cancer metastasis.
In the research, we found that miR-542-3p is decreased in HCC cell lines and tissues, and downregulation of miR-542-3p enhances, while upregulation suppresses HCC cell invasion ability. Further assay demonstrated that miR-542-3p can directly target TGF-β1 3' untranslated region (3'UTR) to influence TGF-β/Smad signaling pathway, and suppression of miR-542-3p can hyperactivate TGF-β/Smad pathway and further to promote Epithelial-Mesenchyme Transition (EMT) and induce poor prognosis. Lastly, the clinical correlation analysis illustrated that miR-542-3p is negatively related with the activity of TGF-β1. In summary, our results find that miR-542-3p takes an important role on HCC progression and provide more evidence of microRNAs (miRNAs) for cancer therapy.
肝细胞癌(HCC)占原发性肝癌的90%以上。尽管在HCC分子机制和治疗技术方面取得了巨大进展,但由于高转移和高复发率,HCC患者的预后仍然很差。
采用定量实时聚合酶链反应(qRT-PCR)对miR-542-3p的表达进行定量分析。使用Transwell和三维培养试验检测miR-542-3p在HCC转移中的作用。采用qRT-PCR、蛋白质免疫印迹法和荧光素酶报告基因检测法阐明miR-542-3p介导癌症转移的机制。
在本研究中,我们发现miR-542-3p在HCC细胞系和组织中表达降低,miR-542-3p的下调增强而其上调则抑制HCC细胞的侵袭能力。进一步的实验表明,miR-542-3p可直接靶向转化生长因子-β1(TGF-β1)的3'非翻译区(3'UTR)以影响TGF-β/ Smad信号通路,抑制miR-542-3p可使TGF-β/ Smad通路过度激活,进而促进上皮-间质转化(EMT)并导致预后不良。最后,临床相关性分析表明miR-542-3p与TGF-β1的活性呈负相关。综上所述,我们的研究结果表明miR-542-3p在HCC进展中发挥重要作用,并为癌症治疗提供了更多关于微小RNA(miRNA)的证据。