Yang Xiaojun, Ye Jing, Yan Han, Tang Zhaoyang, Shen Jian, Zhang Jianping, Yang Lihua
Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jiayuan, Nanjing, 210029, Jiangsu, China.
Department of Gastroenterology, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jiayuan, Nanjing, 210029, Jiangsu, China.
Tumour Biol. 2016 Jan;37(1):201-9. doi: 10.1007/s13277-015-3687-5. Epub 2015 Jul 19.
Hepatocellular carcinoma (HCC) is the most common liver malignancy. Current standard practices for treatment of HCC are less than satisfactory because of CSCs-mediated recurrence. For this reason, targeting CSCs, or cancer cells with CSCs-like properties, is a new approach for HCC treatment. As we reported previously, microRNA-491 (miR-491) is lower expressed in poorly differentiated HCC tissues relative to well-differentiated HCC tissues. Here, we further evaluate the effects of miR-491 on the CSCs-like properties by using HCC cell lines and HCC tissue samples. Our data showed that miR-491 had a negative relationship with CSCs-like properties both in cell lines and tissue samples of HCC. Further, miR-491 levels of non-recurrence HCC tissues were higher than those of recurrence HCC tissues. In HCC cell lines, nuclear factor kappa B (NF-κB)/snail pathway was involved in the epithelial to mesenchymal transition and the maintenance of CSCs-like properties. Overexpression of miR-491 targeted G-protein-coupled receptor kinase-interacting protein 1 (GIT-1), which blocked the activation of NF-κB by the inhibition of extracellular signal-regulated kinases (ERKs). Such process attenuated the CSCs-like properties in HCC cells. Our results point to a previously undefined mechanism by which miR-491 decreases CSCs-like properties and help to identify potential targets for the therapy of HCCs.
肝细胞癌（HCC）是最常见的肝脏恶性肿瘤。由于癌症干细胞（CSCs）介导的复发，目前HCC的标准治疗方法并不令人满意。因此，靶向CSCs或具有CSCs样特性的癌细胞是一种新的HCC治疗方法。正如我们之前报道的，相对于高分化的HCC组织，微小RNA-491（miR-491）在低分化的HCC组织中表达较低。在这里，我们使用HCC细胞系和HCC组织样本进一步评估miR-491对CSCs样特性的影响。我们的数据表明，在HCC的细胞系和组织样本中，miR-491与CSCs样特性呈负相关。此外，非复发性HCC组织中的miR-491水平高于复发性HCC组织。在HCC细胞系中，核因子κB（NF-κB）/蜗牛通路参与上皮-间质转化和CSCs样特性的维持。miR-491的过表达靶向G蛋白偶联受体激酶相互作用蛋白1（GIT-1），通过抑制细胞外信号调节激酶（ERKs）来阻断NF-κB的激活。这样的过程减弱了HCC细胞中的CSCs样特性。我们的结果指出了一种以前未明确的机制，通过该机制miR-491降低了CSCs样特性，并有助于确定HCC治疗的潜在靶点。
