沉默CIT基因可抑制前列腺癌细胞的增殖和转移（英文）

Citron Rho-interacting serine/threonine kinase knockdown suppresses prostate cancer cell proliferation and metastasis by blocking Hippo-YAP pathway

目的探究Citron Rho-interacting serine/threonine kinase(CIT)基因在前列腺癌中的表达特点,并探讨CIT基因对PC-3细胞增殖、迁移和侵袭能力的调控作用及其可能的分子机制。方法利用TCGA和MSKCC数据库分析CIT在前列腺癌组织的表达水平和临床相关性。采用siRNA干扰CIT的表达,采用CCK-8、划痕实验和Transwell实验检测CIT对前列腺癌PC-3细胞系的增殖、迁移和侵袭特性的影响。采用Western blotting检测CIT对上皮-间质转化和Hippo-YAP通路的调控作用。结果 TCGA数据库分析表明,CIT在前列腺癌组织中表达显著上调(P<0.05);MSKCC数据库分析表明,CIT表达水平与N分期(P<0.05)、M分期(P<0.001)、Gleason评分(P=0.010)和PSA水平(P=0.004)成正相关关系。PC-3细胞中沉默CIT表达可显著抑制细胞的增殖、迁移和侵袭,逆转上皮-间质转化进程,并抑制Hippo-YAP通路的激活。结论 CIT基因可能是前列腺癌的致病基因,其分子机制可能与Hippo-YAP通路的激活有关。

Objective Citron Rho-interacting serine/threonine kinase(CIT) was identified recently as an oncogene involved in the progression of various malignant tumors, but its role in prostate cancer(PCa) remains unclear. In this study, we aimed to investigate the biological functions of CIT in PCa. Methods We analyzed the expression of CIT in PCa tissues and its clinical correlations based on the Cancer Genome Atlas(TCGA) and Memorial Sloan-Kettering Cancer Center(MSKCC) dataset. We then examined the effects of RNA interference-mediated CIT silencing on the proliferation, migration and invasion of PC-3 cells using cell counting kit-8,wound healing assay and Transwell assay. We also investigated the effect of CIT silencing on epithelial-mesenchymal transition(EMT) and Hippo-Yap signaling pathway in the cells using Western blotting. Results CIT expression was significantly elevated in PCa tissues from TCGA cohort(P<0.05). MSKCC dataset analysis showed that an elevated expression of CIT was significantly correlated with N stage(P=0.001), distant metastasis(P<0.001), Gleason score(P=0.010) and PSA(P=0.004). In cultured PC-3 cells,knockdown of CIT significantly inhibited cell proliferation, migration and invasion, reversed the EMT phenotype and decreased the expression and activity of YAP. Conclusion CIT might function as an oncogene in PCa by modulating the Hippo-YAP signaling pathway and serve as a candidate therapeutic target for PCa.