Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Department of President's Office, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Cell Cycle. 2022 Feb;21(4):427-438. doi: 10.1080/15384101.2021.2021050. Epub 2022 Jan 2.
Bladder cancer (BC) is one of the most common cancers world-wide with a poor prognosis. Non-SMC (Structural Maintenance of Chromosomes)-condensin I complex subunit H (NCAPH) is a regulatory subunit of the condensin I complex and plays an important role in tumorigenesis and progression in several types of cancers. However, the role of NCAPH in BC remains unknown. In this study, we tried to reveal the biological functions of NCAPH in BC. We detected the expressions of NCAPH in BC and adjacent tissues, and BC cells lines. Subsequently, the gain- and loss-of-function experiments were performed to determine the effects of NCAPH on BC cell proliferation, apoptosis, and activation of the MEK/ERK signaling pathway in vitro. Moreover, we used BALB/c nude mice and established a xenograft model to investigate whether silence NCAPH using shRNA targeting NCAPH (shNCAPH) can inhibit BC tumor growth in vivo. The results showed NCAPH was overexpressed in BC tissues compared to adjacent tissues and highly expressed in BC cell lines. Additionally, overexpression of NCAPH promoted cell proliferation and inhibited apoptosis in SW780 cells. Conversely, knockdown of NCAPH reduced cell proliferation and enhanced apoptosis in UMUC3 cells. Furthermore, we found that the NCAPH activated the MEK/ERK signaling pathway in BC cells. MEK1/2 inhibitor U0126 blocked the increase of cell proliferation regulated by NCAPH overexpression. Knockdown of NCAPH significantly inhibited tumor growth in mice. Our results suggest that NCAPH might play an important role in BC progression and provide the potential marker in the diagnosis of BC.
膀胱癌（BC）是全球最常见的癌症之一，预后较差。非-SMC（染色体结构维持）-凝缩素 I 复合物亚基 H（NCAPH）是凝缩素 I 复合物的调节亚基，在几种类型的癌症的肿瘤发生和进展中发挥重要作用。然而，NCAPH 在 BC 中的作用尚不清楚。在本研究中，我们试图揭示 NCAPH 在 BC 中的生物学功能。我们检测了 BC 和相邻组织以及 BC 细胞系中 NCAPH 的表达。随后，进行了增益和失能实验，以确定 NCAPH 对 BC 细胞增殖、凋亡和 MEK/ERK 信号通路激活的影响。此外，我们使用 BALB/c 裸鼠建立了异种移植模型，以研究使用靶向 NCAPH 的 shRNA（shNCAPH）沉默 NCAPH 是否能抑制体内 BC 肿瘤的生长。结果表明，与相邻组织相比，NCAPH 在 BC 组织中过表达，并且在 BC 细胞系中高表达。此外，NCAPH 的过表达促进了 SW780 细胞的增殖并抑制了凋亡。相反，NCAPH 的敲低降低了 UMUC3 细胞的增殖并增强了凋亡。此外，我们发现 NCAPH 在 BC 细胞中激活了 MEK/ERK 信号通路。MEK1/2 抑制剂 U0126 阻断了由 NCAPH 过表达调节的细胞增殖增加。NCAPH 的敲低显著抑制了小鼠中的肿瘤生长。我们的结果表明，NCAPH 可能在 BC 进展中发挥重要作用，并为 BC 的诊断提供潜在的标志物。
