Local and systemic metastasis of hepatocellular carcinoma (HCC) causes the poor prognosis and increasing evidence confirms that aberrant miRNAs were involved in cancer progression. However, the expression and mechanisms of a specific miR-3194-3p in HCC remains unknown. In this research, we demonstrated that miR-3194-3p, significantly down-regulated in HCC tissues and cell lines, was associated with metastasis and recurrence of HCC. Notably, gain- and loss-of-function assays demonstrated that miR-3194-3p inhibited the migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells in vitro and in vivo. BCL9, up-regulated in HCC tissues, was a direct downstream target of miR-3194-3p and mediated the functional influence of miR-3194-3p. Most importantly, miR-3194-3p exerted its function by regulating β-catenin pathway. Moreover, miR-3194-3p and BCL9 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the down-expression of miR-3194-3p in HCC. Also, the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-3194-3p. Altogether, our study suggested that miR-3194-3p inhibits HCC EMT via decreasing Wnt/β-catenin signaling through targeting BCL9 and might be a therapeutic target for HCC.

中文翻译：

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MicroRNA-3194-3p 通过靶向 BCL9 减少 Wnt/β-catenin 信号传导，抑制肝细胞癌的转移和上皮间充质转化。

肝细胞癌 (HCC) 的局部和全身转移导致预后不良，越来越多的证据证实异常 miRNA 参与了癌症进展。然而，特定 miR-3194-3p 在 HCC 中的表达和机制仍然未知。在这项研究中，我们证明 miR-3194-3p 在 HCC 组织和细胞系中显着下调，与 HCC 的转移和复发有关。值得注意的是，功能获得和功能丧失分析表明 miR-3194-3p 在体外和体内抑制 HCC 细胞的迁移、侵袭和上皮间质转化 (EMT)。BCL9 在 HCC 组织中上调，是 miR-3194-3p 的直接下游靶标并介导 miR-3194-3p 的功能影响。最重要的是，miR-3194-3p 通过调节 β-catenin 通路发挥其功能。而且，miR-3194-3p和BCL9的表达与HCC患者的不良临床特征和不良预后显着相关。我们发现缺氧是导致 HCC 中 miR-3194-3p 下调的原因。此外，缺氧对 HCC 细胞转移和 EMT 的促进作用被 miR-3194-3p 逆转。总之，我们的研究表明 miR-3194-3p 通过靶向 BCL9 降低 Wnt/β-catenin 信号传导来抑制 HCC EMT，并且可能是 HCC 的治疗靶点。