miR-885-5p suppresses hepatocellular carcinoma metastasis and inhibits Wnt/β-catenin signaling pathway.
miR-885-5p suppresses hepatocellular carcinoma metastasis and inhibits Wnt/β-catenin signaling pathway.
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miR-885-5p抑制肝细胞癌转移并抑制Wnt/β-catenin信号通路
DOI：
10.18632/oncotarget.12602
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发表时间：
2016-11-15
期刊：
影响因子：
--
通讯作者：
Xiang R
中科院分区：
文献类型：
--
作者：
Zhang Z;Yin J;Yang J;Shen W;Zhang C;Mou W;Luo J;Yan H;Sun P;Luo Y;Tian Y;Xiang R
微小核糖核酸（miRNA）对肝细胞癌（HCC）的恶性进展具有抑制或促进作用。我们之前报告称，与健康对照组相比，肝硬化患者循环中的miR - 885 - 5p水平最高，其次是慢性乙型肝炎患者和肝细胞癌患者。然而，目前miR - 885 - 5p在肝细胞癌转移中的分子作用尚不清楚。在此，我们证实miR - 885 - 5p的表达与人类肝细胞癌组织样本及细胞系的侵袭和转移能力呈负相关。我们发现，miR - 885 - 5p的表达水平与肝细胞癌患者的生存率相关。miR - 885 - 5p的过表达在体外和体内均降低了肝癌细胞的转移能力。抑制miR - 885 - 5p可促进非转移性肝癌细胞的增殖。此外，我们揭示了miR - 885 - 5p的靶基因是编码β - 连环蛋白的CTNNB1，这导致Wnt / β - 连环蛋白信号通路的活性降低。本研究表明，miR - 885 - 5p通过其靶基因CTNNB1抑制肝细胞癌的转移并抑制Wnt / β - 连环蛋白信号通路，这表明miR - 885 - 5p有望成为肝细胞癌进展的负调控因子以及治疗肝细胞癌的新型治疗药物。
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.