本研究旨在研究细胞分裂调节因子1(PRC1)在胆管癌(CHOL)中的表达,并阐明其潜在的影响以及控制CHOL进展的潜在机制。在这项研究中,我们使用CHOL细胞(HUCCT1,RBE,和CCLP1),并进行了一系列实验,包括qRT-PCR,细胞计数试剂盒-8测定,EdU化验,流式细胞术,伤口愈合试验,Transwell分析,西方印迹,双荧光素酶测定,和ELISA。随后,使用癌细胞注射建立小鼠模型。苏木精-伊红染色,以及Ki67和TUNEL检测,被用来评估组织病理学,细胞增殖,和凋亡。我们的发现揭示了在CHOL中PRC1表达显著升高。根据生物信息学分析,结果发现,PRC1水平升高与高肿瘤等级相关,转移,和不利的预后。值得注意的是,PRC1敲低抑制细胞活力,扩散,迁移,和侵袭,同时促进CHOL细胞凋亡。分析TCGA-CHOL数据并利用转录因子预测工具(hTFtarget和HumanTFDB),我们发现TCGA-CHOL中与PRC1正相关的基因与预测的转录因子相交,显示出叉头盒蛋白M1(FOXM1)对PRC1的激活。此外,根据KEGG和GSEA分析,在CHOL的背景下,发现PRC1对糖酵解和哺乳动物雷帕霉素复合物1(mTORC1)途径具有调节作用。总的来说,这些结果强调了PRC1在CHOL进展中的关键作用,其中它在FOXM1的调节作用下调节糖酵解和mTORC1途径。
This study aimed to investigate the expression of protein regulator of cytokinesis 1 (PRC1) in cholangiocarcinoma (CHOL) and elucidate its potential impact as well as the underlying mechanisms governing the progression of CHOL. In this study, we used CHOL cells (HUCCT1, RBE, and CCLP1) and conducted a series of experiments, including qRT-PCR, cell counting kit-8 assays, EdU assays, flow cytometry, wound healing assays, Transwell assays, western blotting, double luciferase assays, and ELISA. Subsequently, a mouse model was established using cancer cell injections. Haematoxylin-eosin staining, along with Ki67 and TUNEL assays, were employed to assess tissue histopathology, cell proliferation, and apoptosis. Our findings revealed significantly elevated PRC1 expression in CHOL. According to bioinformatics analysis, it was found that the increased PRC1 level is correlated with the high tumour grades, metastases, and unfavourable prognoses. Notably, PRC1 knockdown inhibited cell viability, proliferation, migration, and invasion while promoting apoptosis in CHOL cells. Analysing TCGA-CHOL data and utilising transcription factor prediction tools (hTFtarget and HumanTFDB), we identified that genes positively correlated with PRC1 in TCGA-CHOL intersect with predicted transcription factors, revealing the activation of PRC1 by forkhead box protein M1 (FOXM1). Moreover, PRC1 was found to exert regulatory control over glycolysis and the mammalian target of rapamycin complex 1 (mTORC1) pathway in the context of CHOL based on KEGG and GSEA analysis. Collectively, these results underscore the pivotal role of PRC1 in CHOL progression, wherein it modulates glycolysis and the mTORC1 pathway under the regulatory influence of FOXM1.