Chen Bingqing, Liao Zhibin, Qi Yongqiang, Zhang Hongwei, Su Chen, Liang Huifang, Zhang Bixiang, Chen Xiaoping
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Science and Technology Department of Hubei Province, Wuhan, China.
Front Oncol. 2020 Dec 4;10:565266. doi: 10.3389/fonc.2020.565266. eCollection 2020.
MicroRNAs (miRNAs) have been reported to play critical roles in the pathological development of hepatocellular carcinoma (HCC), one of the most common cancers in the world. Our study aims to explore the expression, function and mechanism of miR-631 in HCC. Our findings are that expression of miR-631 is significantly down-regulated in HCC tissue compared with that in adjacent non-cancerous tissue, and low expression of miR-631 in HCC tissue is associated with cirrhosis, multiple tumors, incomplete tumor encapsulation, poor tumor differentiation, and high TNM stage. Our test results showed that miR-631 could inhibit migration, invasion, epithelial-mesenchymal transition (EMT) and intrahepatic metastasis of HCC. Receptor-type protein tyrosine phosphatase epsilon (PTPRE) as a downstream target of miR-631 could promote migration, invasion and EMT of HCC cells. Besides, the expression of PTPRE had a negative correlation with the expression of miR-631 both and , and increasing expression of PTPRE could reverse inhibitory effects of miR-631 in HCC cells. In sum, our study first demonstrated that miR-631 targeted PTPRE to inhibit intrahepatic metastasis in HCC. We gain insights from these findings into the mechanism of miRNAs regulation in HCC metastasis and further introduce a novel therapeutic target for HCC treatment.
据报道，微小RNA（miRNA）在肝细胞癌（HCC）的病理发展过程中发挥着关键作用，HCC是全球最常见的癌症之一。我们的研究旨在探讨miR-631在HCC中的表达、功能及机制。我们的研究结果显示，与癌旁非癌组织相比，miR-631在HCC组织中的表达显著下调，且HCC组织中miR-631的低表达与肝硬化、多发肿瘤、肿瘤包膜不完整、肿瘤分化差及高TNM分期相关。我们的检测结果表明，miR-631可抑制HCC的迁移、侵袭、上皮-间质转化（EMT）及肝内转移。作为miR-631下游靶点的受体型蛋白酪氨酸磷酸酶ε（PTPRE）可促进HCC细胞的迁移、侵袭及EMT。此外，PTPRE的表达在mRNA和蛋白水平均与miR-631的表达呈负相关，且PTPRE表达的增加可逆转miR-631对HCC细胞的抑制作用。总之，我们的研究首次证明miR-631通过靶向PTPRE抑制HCC的肝内转移。我们从这些发现中深入了解了miRNA调控HCC转移的机制，并进一步为HCC治疗引入了一个新的治疗靶点。
