目的：探讨剪接因子3b亚基6（splicing factor 3b subunit 6，SF3b6）对胃癌细胞增殖、凋亡、侵袭和迁移等的影响及其作用机制。方法：通过组织芯片检测 SF3b6 在胃癌和癌旁组织中的表达，采用 WB 和 qPCR检测SF3b6在正常永生化胃上皮细胞(GES-1)和胃癌细胞系(HGC27、AGS、BGC823、MGC803、SGC7901、MKN45)中的表达水平。选取AGS和MGC803细胞转染SF3b6-siRNA、BGC823和SGC7901细胞转染SF3b6过表达质粒进行功能实验，CCK-8实验检测SF3b6对胃癌细胞增殖的影响，Transwell迁移和侵袭实验检测SF3b6对胃癌细胞迁移和侵袭能力的影响，流式细胞术检测细胞凋亡水平，WB检测凋亡和迁移相关分子及MAPK信号分子在蛋白水平的变化。结果:SF3b6在胃癌细胞MGC803和AGS表达水平高于正常胃上皮细胞GES-1，而在BGC823和SGC7901细胞中低于GES-1细胞（P<0.05或P<0.01）。敲低SF3b6的表达抑制了胃癌细胞系AGS和MGC803的增殖、迁移和侵袭，并促进了细胞凋亡（P<0.05或P<0.01）；过表达SF3b6促进了胃癌细胞系BGC823和SGC7901的增殖、迁移和侵袭（P<0.05或P<0.01）。机制研究表明，敲低SF3b6表达促进了JNK 和 P38 的活化，以及凋亡相关蛋白 cleaved caspase-9、cleaved PARP、Bax的表达（P<0.05或P<0.01），同时抑制胃癌细胞上皮间质转化的进程。结论：剪接因子SF3b6通过MAPK信号通路增强胃癌细胞增殖和迁移，促进胃癌的发展进程。

Objective: To explore the effect and mechanism of splicing factor 3b subunit 6 (SF3b6) on the proliferation, apoptosis,invasion and migration of gastric cancer cells. Methods: Tissue microarrays were used to detect the expression of SF3b6 in gastric cancer tissues and adjacent tissues. WB and qPCR were used to detect the expression of SF3b6 in normal immortalized gastric epithelial cells (GES-1) and gastric cancer cell lines (HGC27, AGS, BGC823, MGC803, SGC7901, MKN45). AGS and MGC803 cells were transfected with SF3b6 siRNA, and BGC823 and SGC7901 cells were transfected with SF3b6 over-expression plasmid for functional experiments. CCK-8 assay was used to detect the regulation of SF3b6 on the proliferation of gastric cancer cells; Transwell migration and invasion experiments were used to detect the effect of SF3b6 on the migration and invasion of gastric cancer cells; Flow cytometry was used to detect cell apoptosis; and WB was adopted to detect expressions of apoptosis and migration-related molecules and MAPK signaling pathway associated proteins. Results: The expression level of SF3b6 in gastric cancer MGC803 and AGS cells was significantly higher while in BGC823 and SGC7901 cells was significantly lower than that in normal gastric epithelial GES-1 cells (P<0.05 or P<0.01). SF3b6 knockdown inhibited the proliferation, migration and invasion, but promoted cell apoptosis of gastric cancer cell lines AGS and MGC803 (P<0.05 or P<0.01); However, over-expression of SF3b6 promoted the proliferation, migration and invasion of gastric cancer cell lines BGC823 and SGC7901 (P<0.05 or P<0.01). Mechanism study showed that SF3b6 knockdown promoted the activation of JNK and p38 and expression of apoptosis-related protein cleaved caspase-9, cleaved PARP and Bax (P<0.05 or P<0.01), and meanwhile inhibited the process of epithelial to mesenchymal transition (EMT) in gastric cancer cells. Conclusion:The splicing factor SF3b6 enhances cell proliferation and migration via MAPK signaling pathway, thereby promoting tumor progression.

国家自然科学基金资助项目（No. 31770944）