目的探讨谷氨酸-脯氨酸-亮氨酸富集蛋白1(proline-,glutamic acid-,and leucine-rich protein 1,PELP1)在胃癌中的生物学功能及临床意义。方法通过生物信息学方法分析PELP1在胃癌中的表达,并在胃癌细胞系和胃癌临床样本中予以验证,Kapla...目的探讨谷氨酸-脯氨酸-亮氨酸富集蛋白1(proline-,glutamic acid-,and leucine-rich protein 1,PELP1)在胃癌中的生物学功能及临床意义。方法通过生物信息学方法分析PELP1在胃癌中的表达,并在胃癌细胞系和胃癌临床样本中予以验证,Kaplan-Meier生存分析探讨PELP1表达与胃癌患者生存预后的关系。以siRNA敲降胃癌细胞AGS中的PELP1表达,以CCK-8实验、平板克隆形成实验、EdU细胞增殖实验检测细胞增殖活性;流式细胞术测定细胞周期;细胞划痕实验、Transwell小室检测细胞迁移、侵袭能力。Western blot和qRT-PCR检测敲降PELP1表达的AGS细胞中Src-Erk通路信号分子表达情况。结果PELP1在胃癌组织中表达相对较高,生存分析显示PELP1高表达的患者生存期更短;敲降PELP1表达后的胃癌细胞增殖、迁移、侵袭等恶性生物学行为均受到抑制;敲降PELP1表达的AGS细胞,其Src-Erk通路关键信号分子c-Src、PI3K和Erk的表达均降低。结论PELP1在胃癌的发生发展中起致瘤作用,可能是胃癌潜在的治疗靶点。展开更多
FXYD6, FXYD domain containing ion transport regulator 6, has been reported to affect the activity of Na＋/K＋-ATP- ase and be associated with mental diseases. Here, we demonstrate that FXYD6 is up-regulated in hepatoc...FXYD6, FXYD domain containing ion transport regulator 6, has been reported to affect the activity of Na＋/K＋-ATP- ase and be associated with mental diseases. Here, we demonstrate that FXYD6 is up-regulated in hepatocellular carcinoma （HCC） and enhances the migration and prolif- eration of HCC cells. Up-regulation of FXYD6 not only positively correlates with the increase of Na＋IK＋-ATPase but also coordinates with the activation of its downstream Src-ERK signaling pathway. More importantly, blocking FXYD6 by its functional antibody significantly inhibits the growth potential of the xenografted HCC tumors in mice, indicating that FXYD6 represents a potential therapeutic target toward HCC. Altogether, our results establish a critical role of FXYD6 in HCC progression and suggest that the therapy targeting FXYD6 can benefit the clinical treatment toward HCC patients.展开更多
文摘FXYD6, FXYD domain containing ion transport regulator 6, has been reported to affect the activity of Na＋/K＋-ATP- ase and be associated with mental diseases. Here, we demonstrate that FXYD6 is up-regulated in hepatocellular carcinoma （HCC） and enhances the migration and prolif- eration of HCC cells. Up-regulation of FXYD6 not only positively correlates with the increase of Na＋IK＋-ATPase but also coordinates with the activation of its downstream Src-ERK signaling pathway. More importantly, blocking FXYD6 by its functional antibody significantly inhibits the growth potential of the xenografted HCC tumors in mice, indicating that FXYD6 represents a potential therapeutic target toward HCC. Altogether, our results establish a critical role of FXYD6 in HCC progression and suggest that the therapy targeting FXYD6 can benefit the clinical treatment toward HCC patients.
