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MicroRNA-3194-3p 通过靶向 BCL9 降低 Wnt/β-catenin 信号通路抑制肝癌转移和上皮间质转化。

MicroRNA-3194-3p inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by decreasing Wnt/β-catenin signaling through targeting BCL9.

机构信息

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.

出版信息

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3885-3895. doi: 10.1080/21691401.2019.1670190.

Abstract

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.

摘要

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。

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