R-spondin 2 promotes proliferation and migration via the Wnt/β-catenin pathway in human hepatocellular carcinoma.
R-spondin 2 promotes proliferation and migration via the Wnt/β-catenin pathway in human hepatocellular carcinoma.
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R-spondin 2 通过 Wnt/β-catenin 通路促进人肝细胞癌的增殖和迁移。
DOI：
10.3892/ol.2017.6339
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发表时间：
2017
期刊：
影响因子：
2.9
通讯作者：
Linghua Yu
中科院分区：
文献类型：
--
作者：
Xinguang Yin;Huixing Yi;Linlin Wang;Wan;Xiaojun Wu;Linghua Yu
肝细胞癌（HCC）是恶性疾病相关死亡的主要原因，特别是在中国。 RSPO2 (R-spondin 2) 基因在脊椎动物中进化保守，参与发育和生理过程。重要的是，据报道 RSPO2 与结肠癌相关并增强 Wnt/β-catenin 信号通路。在本研究中，使用组织微阵列观察到 HCC 中 RSPO2 表达的增强。同样，与人正常QSG7701肝细胞相比，RSPO2的表达水平在HepG2、Huh7和Hep3B细胞中较高，但在Bel7404和QGY7703细胞中较低。随后，功能获得研究表明，RSPO2 基于慢病毒基因传递促进 QGY7703 细胞的增殖和迁移。此外，研究还表明，QGY7703细胞中RSPO2的功能涉及p21和瘦素，而不是血管内皮生长因子-A。特别是，信号转导子和转录激活子 3 (STAT3) 和 Wnt/β-catenin 信号通路参与了这一过程。 RSPO2 的过度表达导致磷酸化 STAT3、β-catenin 和 c-Myc 的表达升高。因此，本研究有助于了解RSPO2参与的肝癌转化和药物发现。
Hepatocellular carcinoma (HCC) is a leading cause of malignant disease-associated mortality, particularly in China. The RSPO2 (R-spondin 2) gene is evolutionarily conserved in vertebrates and is involved in developmental and physiological processes. Importantly, RSPO2 has been reported to be associated with colon cancer and potentiate the Wnt/β-catenin signaling pathway. In the present study, enhanced expression of RSPO2 in HCC was observed using tissue microarray. Similarly, the expression level of RSPO2 was higher in HepG2, Huh7 and Hep3B cells but lower in Bel7404 and QGY7703 cells compared with human normal QSG7701 liver cells. Subsequently, gain-of-function studies indicated that RSPO2 promotes the proliferation and migration of QGY7703 cells based on lentivirus-based gene delivery. Furthermore, it was revealed that p21 and leptin, rather than vascular endothelial growth factor-A, are involved in the function of RSPO2 in QGY7703 cells. Particularly, the signal transducer and activator of transcription 3 (STAT3) and Wnt/β-catenin signaling pathways are involved in this process. Overexpression of RSPO2 resulted in the elevated expression of phosphorylated STAT3, β-catenin and c-Myc. Therefore, the present study is beneficial to the understanding of RSPO2-involved liver cancer transformation and drug discovery.
影响因子：
64.5
作者：
H. Clevers
通讯作者：
H. Clevers
影响因子：
29.4
作者：
Monga SP
通讯作者：
Monga SP