Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Mol Cells. 2018 Sep 30;41(9):830-841. doi: 10.14348/molcells.2018.0181. Epub 2018 Aug 27.
Recent studies have indicated that microRNAs (miRNAs) play an important role in hepatocellular carcinoma (HCC) progression. In this study, we showed that miR-766-3p was decreased in approximately 72% of HCC tissues and cell lines, and its low expression level was significantly correlated with tumour size, TNM stage, metastasis, and poor prognosis in HCC. Ectopic miR-766-3p expression inhibited HCC cell proliferation, colony formation, migration and invasion. In addition, we showed that miR-766-3p repressed Wnt3a expression. A luciferase reporter assay revealed that Wnt3a was a direct target of miR-766-3p, and an inverse correlation between miR-766-3p and Wnt3a expression was observed. Moreover, Wnt3a up-regulation reversed the effects of miR-766-3p on HCC progression. In addition, our study showed that miR-766-3p up-regulation decreased the nuclear β-catenin level and expression of Wnt targets (TCF1 and Survivin) and reduced the level of MAP protein regulator of cytokinesis 1 (PRC1). However, these effects of miR-766-3p were reversed by Wnt3a up-regulation. In addition, PRC1 up-regulation increased the nuclear β-catenin level and protein expression of TCF1 and Survivin. iCRT3, which disrupts the β-catenin-TCF4 interaction, repressed the TCF1, Survivin and PRC1 protein levels. Taken together, our results suggest that miR-766-3p down-regulation promotes HCC cell progression, probably by targeting the Wnt3a/PRC1 pathway, and miR-766-3p may serve as a potential therapeutic target in HCC.
最近的研究表明，微小 RNA（miRNA）在肝细胞癌（HCC）进展中发挥重要作用。在本研究中，我们表明 miR-766-3p 在大约 72%的 HCC 组织和细胞系中表达下调，其低表达水平与 HCC 中的肿瘤大小、TNM 分期、转移和预后不良显著相关。外源性 miR-766-3p 表达抑制 HCC 细胞增殖、集落形成、迁移和侵袭。此外，我们表明 miR-766-3p 抑制 Wnt3a 的表达。荧光素酶报告基因检测表明 Wnt3a 是 miR-766-3p 的直接靶基因，miR-766-3p 与 Wnt3a 表达呈负相关。此外，Wnt3a 的上调逆转了 miR-766-3p 对 HCC 进展的影响。此外，我们的研究表明，miR-766-3p 的上调降低了核 β-连环蛋白水平和 Wnt 靶基因（TCF1 和 Survivin）的表达，并降低了细胞分裂调控因子 1（PRC1）的蛋白水平。然而，这些 miR-766-3p 的作用被 Wnt3a 的上调所逆转。此外，PRC1 的上调增加了核 β-连环蛋白水平和 TCF1 和 Survivin 的蛋白表达。iCRT3 破坏了 β-连环蛋白-TCF4 相互作用，抑制了 TCF1、Survivin 和 PRC1 蛋白水平。综上所述，我们的研究结果表明，miR-766-3p 的下调促进了 HCC 细胞的进展，可能是通过靶向 Wnt3a/PRC1 通路，miR-766-3p 可能作为 HCC 的潜在治疗靶点。
