miR-766-3p Targeting BCL9L Suppressed Tumorigenesis, Epithelial-Mesenchymal Transition, and Metastasis Through the β-Catenin Signaling Pathway in Osteosarcoma Cells.
miR-766-3p Targeting BCL9L Suppressed Tumorigenesis, Epithelial-Mesenchymal Transition, and Metastasis Through the β-Catenin Signaling Pathway in Osteosarcoma Cells.
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miR-766-3p 靶向 BCL9L 通过 b-Catenin 信号通路抑制骨肉瘤细胞的肿瘤发生、上皮间质转化和转移
DOI：
10.3389/fcell.2020.594135
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发表时间：
2020
影响因子：
5.5
通讯作者：
Cao X
中科院分区：
文献类型：
--
作者：
Zhang S;Chen H;Liu W;Fang L;Qian Z;Kong R;Zhang Q;Li J;Cao X
越来越多的证据表明，异常microRNAs （miRNAs）在骨肉瘤（OS）的癌变和发展中起着关键作用。本研究旨在阐明miR-766-3p与骨肉瘤发生发展的关系，并探讨其可能的机制。在本研究中，我们通过分析GEO数据库中的GSE65071，发现miR-766-3p是下调最多的miRNA。miR-766-3p在OS组织样本和细胞中低表达，高表达miR-766-3p在体外和体内抑制OS的恶性水平，包括细胞增殖、EMT、迁移和侵袭。在OS细胞和组织样本中，b细胞淋巴瘤9样蛋白（BCL9L）与miR-766-3p的表达呈负相关，并通过荧光素酶报告基因实验和western blotting验证了BCL9L是下游靶点。挽救实验表明，BCL9L可以恢复miR-766-3p对OS细胞的影响。此外，β-Catenin/TCF-4信号通路被证明与miR-766-3p/BCL9L轴有关。综上所述，BCL9L的负调节因子miR-766-3p在OS的进展中通过β-catenin信号通路发挥肿瘤转移抑制因子的作用。
Accumulating evidence has indicated that abnormal microRNAs (miRNAs) serve critical roles in carcinogenesis and development of osteosarcoma (OS). The purpose of the present study was to elucidate the relationship between miR-766-3p and development of osteosarcoma and explore the potential mechanism. In this study, we found that miR-766-3p was the most downregulated miRNA by analyzing GSE65071 from the GEO database. miR-766-3p was lowly expressed in OS tissue samples and cells, and high miR-766-3p expression repressed the malignant level of OS, including cell proliferation, EMT, migration, and invasion in vitro and in vivo. B-Cell Lymphoma 9-Like Protein (BCL9L) was negatively associated with miR-766-3p expression in OS cells and tissue samples and was validated as the downstream target by luciferase reporter assay and western blotting. Rescue experiment indicated that BCL9L could restore the influence of miR-766-3p on OS cells. In addition, the β-Catenin/TCF-4 signal pathway was demonstrated to be related to the miR-766-3p/BCL9L axis. In summary, miR-766-3p, a negative regulator of BCL9L, plays the role of tumor metastasis suppressor via the β-catenin signaling pathway in the progression of OS.