Chen Xuanrong, Shao Yi, Li Yang, Yang Zhao, Chen Yutong, Yu Wenyue, Shang Zhiqun, Wei Wanqing
Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Department of Pediatric Surgery, Huai'an Maternal and Children Health Hospital, Huai'an, China.
Transl Cancer Res. 2022 May;11(5):1099-1111. doi: 10.21037/tcr-21-2164.
The cell cycle gene centromere protein K () is upregulated in various cancers; however, the clinical value and mechanism of in prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) remain unclear.
The expression of in PCa was analyzed in both patients with PCa and cell lines using immunohistochemistry (IHC), real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and bioinformatics analyses. Knockdown of in PCa cells was achieved by transfecting siRNAs and assessed using qRT-PCR and Western blotting. MTT and colony formation assays were used to assess the growth of PCa cells. The cell cycle was analyzed using propidium iodide (PI) staining and flow cytometry. To study the possible biological function of , pathway enrichment analysis was performed by dividing these groups into a high expression group and a low expression group based on the median expression level. Finally, the correlation between expression in PCa and clinical parameters was evaluated.
Our study revealed that was expressed at high levels in CRPC tissues and cell lines compared to primary PCa. The downregulation of significantly inhibited cell viability and reduced the number of colonies formed by LNCaP-AI and DU145 cells (two CRPC cell lines). Gene enrichment and flow cytometry analyses showed that high expression was linked to mitotic spindles and the cell cycle and may be involved in mitosis in the cell cycle of cancer cells to modulate cell proliferation and promote the development of CRPC. Moreover, patients exhibiting higher expression of the mRNA experienced shorter disease-free survival (DFS) and overall survival (OS) than the lower expression group.
This study provides novel molecular insights into the role of in castration-resistant PCa cells and reveals that an increase in expression may indicate shorter DFS and a poor prognosis for patients with PCa. Targeting may be a novel strategy for the treatment of PCa.
细胞周期基因着丝粒蛋白K（）在多种癌症中上调；然而，其在前列腺癌（PCa）和去势抵抗性前列腺癌（CRPC）中的临床价值和机制仍不清楚。
采用免疫组织化学（IHC）、实时定量逆转录PCR（qRT-PCR）、蛋白质免疫印迹法和生物信息学分析，对PCa患者和细胞系中该基因的表达进行分析。通过转染小干扰RNA（siRNAs）实现PCa细胞中该基因的敲低，并使用qRT-PCR和蛋白质免疫印迹法进行评估。采用MTT和集落形成试验评估PCa细胞的生长。使用碘化丙啶（PI）染色和流式细胞术分析细胞周期。为了研究该基因可能的生物学功能，根据该基因表达水平的中位数将这些组分为高表达组和低表达组，进行通路富集分析。最后，评估PCa中该基因表达与临床参数之间的相关性。
我们的研究表明，与原发性PCa相比，CRPC组织和细胞系中该基因高水平表达。该基因的下调显著抑制细胞活力，并减少LNCaP-AI和DU145细胞（两种CRPC细胞系）形成的集落数量。基因富集和流式细胞术分析表明，该基因的高表达与有丝分裂纺锤体和细胞周期相关，可能参与癌细胞细胞周期中的有丝分裂，以调节细胞增殖并促进CRPC的发展。此外，与低表达组相比，该基因mRNA表达较高的患者无病生存期（DFS）和总生存期（OS）较短。
本研究为该基因在去势抵抗性PCa细胞中的作用提供了新的分子见解，并表明该基因表达增加可能预示PCa患者DFS较短且预后不良。靶向该基因可能是治疗PCa的新策略。
