Zhang Zhuhong, Yin Jing, Yang Jian, Shen Wenzhi, Zhang Chunyan, Mou Wenjun, Luo Jinhua, Yan Hua, Sun Peiqing, Luo Yunping, Tian Yaping, Xiang Rong
Department of Immunology, School of Medicine, Nankai University, Tianjin, 300071, China.
Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Oncotarget. 2016 Nov 15;7(46):75038-75051. doi: 10.18632/oncotarget.12602.
MicroRNAs (miRNAs) inhibit or improve the malignant progression of hepatocellular carcinoma (HCC). We previously reported that compared to health controls, patients with liver cirrhosis present the highest levels of circulating miR-885-5p, followed by those with chronic hepatitis B and those with HCC. However, the molecular involvement of miR-885-5p in HCC metastasis is presently unclear. Here, we demonstrated that the expression of miR-885-5p negatively correlated with the invasive and metastatic capabilities of human HCC tissue samples and cell lines. We found that miR-885-5p expression levels correlated with the survival of patients with HCC. Overexpression of miR-885-5p decreased metastasis of HCC cells in vitro and in vivo. Inhibition of miR-885-5p improved proliferation of non-metastatic HCC cells. Furthermore, we disclosed that miR-885-5p targeted gene encoding β-catenin CTNNB1, leading to decreased activity of the Wnt/β-catenin signaling pathway. The present study indicates that miR-885-5p suppresses the metastasis of HCC and inhibits Wnt/β-catenin signaling pathway by its CTNNB1 target, which suggests that miR-885-5p to be a promising negative regulator of HCC progression and as a novel therapeutic agent to treat HCC.
微小RNA（miRNA）可抑制或促进肝细胞癌（HCC）的恶性进展。我们之前报道过，与健康对照相比，肝硬化患者循环miR-885-5p水平最高，其次是慢性乙型肝炎患者和HCC患者。然而，目前尚不清楚miR-885-5p在HCC转移中的分子机制。在此，我们证明miR-885-5p的表达与人类HCC组织样本和细胞系的侵袭和转移能力呈负相关。我们发现miR-885-5p表达水平与HCC患者的生存率相关。miR-885-5p的过表达在体外和体内均降低了HCC细胞的转移。抑制miR-885-5p可促进非转移性HCC细胞的增殖。此外，我们发现miR-885-5p靶向编码β-连环蛋白CTNNB1的基因，导致Wnt/β-连环蛋白信号通路活性降低。本研究表明，miR-885-5p通过其CTNNB1靶点抑制HCC转移并抑制Wnt/β-连环蛋白信号通路，这表明miR-885-5p有望成为HCC进展的负调控因子和治疗HCC的新型治疗药物。
