Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.
Translational Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3885-3895. doi: 10.1080/21691401.2019.1670190.
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 and . 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.
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,异常的miRNA 参与了癌症的进展。然而,miR-3194-3p 在 HCC 中的表达和机制尚不清楚。在这项研究中,我们证明了 miR-3194-3p 在 HCC 组织和细胞系中显著下调,与 HCC 的转移和复发有关。值得注意的是,增益和缺失功能实验表明,miR-3194-3p 抑制了 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,并介导了 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。此外,miR-3194-3p 和 BCL9 的表达与 HCC 患者不良的临床特征和预后密切相关。我们表明,缺氧是 HCC 中 miR-3194-3p 下调的原因。此外,miR-3194-3p 逆转了缺氧对 HCC 细胞转移和 EMT 的促进作用。总之,我们的研究表明,miR-3194-3p 通过靶向 BCL9 减少 Wnt/β-catenin 信号通路抑制 HCC EMT,可能是 HCC 的治疗靶点。