Metformin Suppresses Hepatocellular Carcinoma through Regulating Alternative Splicing of LGR4.
Metformin Suppresses Hepatocellular Carcinoma through Regulating Alternative Splicing of LGR4.
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首先，采用免疫印迹和免疫荧光法检测LGR 4在肝癌组织和细胞系中的表达。用CCK 8、创伤愈合和transwell试验检测过表达LGR 4或用二甲双胍处理时细胞增殖、迁移和侵袭的能力。免疫荧光法检测β-catenin的表达。为了研究新的AS相关LGR 4，我们从GSO数据库中丢弃了LGR 4亚型。我们使用siRNA敲除特定的同种型，以检查二甲双胍治疗时的细胞增殖、迁移和侵袭。 LGR 4在肝癌细胞系和肿瘤组织中的表达水平较高。当LGR 4过表达时，HCC细胞的增殖、迁移和侵袭增加，二甲双胍治疗可以降低这种增加。GEO数据库（GSE 190076）显示，LGR 4在二甲双胍处理的HCC细胞系中具有转换特性。我们利用siRNA敲除特异性异构体，结果显示特异性异构体siRNA可以促进二甲双胍对细胞侵袭的抑制作用。 LGR 4可促进肝癌细胞的增殖、迁移和侵袭能力，二甲双胍可通过选择性剪接降低LGR 4的增殖、迁移和侵袭能力。
First, the expression of LGR4 in HCC tumor tissues and cell lines was detected by western blotting and immunofluorescence. The ability of cell proliferation, migration, and invasion was detected with CCK8, wound-healing, and transwell assays when overexpressing LGR4 or treating with metformin. The β-catenin expression was detected by immunofluorescence. In order to investigate novel AS-associated LGR4, we discarded LGR4 isoforms from GSO databases. We used siRNA to knock down the specific isoform to check the cell proliferation, migration, and invasion when treated with metformin. The level of LGR4 expression was higher in HCC cell lines and tumor tissues. The HCC cell proliferation, migration, and invasion were increased when overexpressing LGR4, which could be reduced by metformin treatment. The GEO database (GSE190076) showed that LGR4 had switching properties in HCC cell lines treated with metformin. We used siRNA to knock down the specific isoform, and the result showed that the specific isoform siRNA could promote the inhibition of cell invasion caused by metformin treatment. LGR4 could promote the ability of cell proliferation, migration, and invasion in HCC, which could be reduced by metformin through alternative splicing.
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影响因子：
4.6
作者：
Tarhini, Zeinab;Manceur, Kamelia;Magne, Julien;Mathonnet, Muriel;Jost, Jeremy;Christou, Niki
通讯作者：
Christou, Niki
影响因子：
4.1
作者：
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通讯作者：
Lee YH
影响因子：
5.6
作者：
通讯作者：
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影响因子：
5.6
作者：
Ordaz-Ramos A;Rosales-Gallegos VH;Melendez-Zajgla J;Maldonado V;Vazquez-Santillan K
通讯作者：
Vazquez-Santillan K
影响因子：
9.7
作者：
Cheng, Qi;Zheng, Hao;Du, Lei
通讯作者：
Du, Lei