RCC2 通过 Hh/GLI1 信号通路和癌症干细胞样细胞促进前列腺癌细胞增殖和迁移。
RCC2 promotes prostate cancer cell proliferation and migration through Hh/GLI1 signaling pathway and cancer stem-like cells.
机构信息
Department of Urology, Aerospace Center Hospital, No.15, Yuquan Road, Haidian District, Beijing, 100049, China.
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
出版信息
Biol Direct. 2023 Nov 27;18(1):80. doi: 10.1186/s13062-023-00439-w.
BACKGROUND
Regulator of chromosome condensation 2 (RCC2) was a telophase disk-binding protein on mitosis, and functions as an oncogene in many human cancers. However, its role on prostate cancer (PCa) was unknown. The goal of this study is to explore the function of RCC 2 on PCa development.
METHODS
The expression of RCC2 and its methylation level, its correlation with lymph node metastasis or disease-free survival (DFS) was analyzed using TCGA database. The effect of RCC2 on PCa cell proliferation, migration and invasion were detected using CCK-8, cell colony formation, Transwell and wood healing assays. RNA-seq and GSEA analysis were used to search the downstream genes and pathways of RCC2 in mediated PCa progression. Western blot was used to detect the proteins in PCa cells transfected with indicated siRNAs or plasmids.
RESULTS
RCC2 had high expression and low promoter methylation level in PCa, and its expression was correlated with regional node metastasis and disease-free survival. Cell proliferation, migration, invasion and EMT of PCa cells in vitro were greatly enhanced after RCC2 overexpression, while the RCC2 knockdown suppressed these processes. RNA-seq and GSEA results showed the Hedgehog signaling regulator Gli1 and Gli3 were involved in RCC2 knockdown DU145 cells. Gli1 was also a marker of cancer stem-like cells (CSCs). Mechanistically, RCC2 induced cell growth, EMT, CSCs markers through Gli1; inhibiting Gli1 expression using siGli1 or GLI inhibitor suppressed cell progression in vitro and tumor growth in vivo.
CONCLUSION
In summary, RCC2 promoted PCa development through Hh/Gli1 signaling pathway via regulating EMT and CSCs.
背景
染色体凝聚调控因子 2（RCC2）是有丝分裂末期盘结合蛋白，在许多人类癌症中作为癌基因发挥作用。然而，其在前列腺癌（PCa）中的作用尚不清楚。本研究旨在探讨 RCC2 对前列腺癌发展的作用。
方法
利用 TCGA 数据库分析 RCC2 的表达及其甲基化水平，及其与淋巴结转移或无病生存（DFS）的相关性。使用 CCK-8、细胞集落形成、Transwell 和木愈合测定法检测 RCC2 对 PCa 细胞增殖、迁移和侵袭的影响。使用 RNA-seq 和 GSEA 分析来搜索 RCC2 在介导 PCa 进展中的下游基因和途径。使用 Western blot 检测转染了指示性 siRNAs 或质粒的 PCa 细胞中的蛋白质。
结果
RCC2 在 PCa 中表达水平较高，启动子低甲基化，其表达与局部淋巴结转移和无病生存相关。体外过表达 RCC2 后，PCa 细胞的增殖、迁移、侵袭和 EMT 大大增强，而 RCC2 敲低则抑制了这些过程。RNA-seq 和 GSEA 结果表明 Hedgehog 信号调节因子 Gli1 和 Gli3 参与了 RCC2 敲低 DU145 细胞。Gli1 也是癌症干细胞样细胞（CSCs）的标志物。在机制上，RCC2 通过 Gli1 诱导细胞生长、EMT 和 CSCs 标志物；使用 siGli1 或 GLI 抑制剂抑制 Gli1 表达可抑制体外细胞进展和体内肿瘤生长。
结论
总之，RCC2 通过 Hh/Gli1 信号通路促进 PCa 的发展，该通路通过调节 EMT 和 CSCs。
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