Department of Urology, Shenjing Hospital of China Medical University, Shenyang, China.
Department of Urology, The First Hospital of China Medical University, Shenyang, China.
J Transl Med. 2024 Jan 2;22(1):12. doi: 10.1186/s12967-023-04834-9.
Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men worldwide, and its incidence has risen substantially in recent years. Therefore, there is an urgent need to identify novel biomarkers and precise therapeutic targets for managing PCa progression and recurrence.
We investigated the clinical significance of NCAPG2 in PCa by exploring public datasets and our tissue microarray. Receiver operating characteristic (ROC) curve and survival analyses were performed to evaluate the correlation between NCAPG2 and PCa progression. Cell proliferation, wound healing, transwell, flow cytometry, cell cycle, tumor sphere formation, immunofluorescence (IF), co-immunoprecipitation (co-IP), and chromatin immunoprecipitation (ChIP) assays were conducted to further elucidate the molecular mechanism of NCAPG2 in PCa. Subcutaneous and orthotopic xenograft models were applied to investigate the effects of NCAPG2 on PCa proliferation in vivo. Tandem mass tag (TMT) quantitative proteomics was utilized to detect proteomic changes under NCAPG2 overexpression.
NCAPG2 was significantly upregulated in PCa, and its overexpression was associated with PCa progression and unfavorable prognosis. Knockdown of NCAPG2 inhibited the malignant behavior of PCa cells, whereas its overexpression promoted PCa aggressiveness. NCAPG2 depletion attenuated the development and growth of PCa in vivo. TMT quantitative proteomics analyses indicated that c-MYC activity was strongly correlated with NCAPG2 expression. The malignancy-promoting effect of NCAPG2 in PCa was mediated via c-MYC. NCAPG2 could directly bind to STAT3 and induce STAT3 occupancy on the MYC promoter, thus to transcriptionally activate c-MYC expression. Finally, we identified that NCAPG2 was positively correlated with cancer stem cell (CSC) markers and enhanced self-renewal capacity of PCa cells.
NCAPG2 is highly expressed in PCa, and its level is significantly associated with PCa prognosis. NCAPG2 promotes PCa malignancy and drives cancer stemness via the STAT3/c-MYC signaling axis, highlighting its potential as a therapeutic target for PCa.
前列腺癌（PCa）是全球男性癌症相关死亡的第二大主要原因，近年来其发病率显著上升。因此，迫切需要确定用于管理 PCa 进展和复发的新型生物标志物和精确治疗靶点。
通过探索公共数据集和我们的组织微阵列，研究了 NCAPG2 在 PCa 中的临床意义。进行了接收者操作特征（ROC）曲线和生存分析，以评估 NCAPG2 与 PCa 进展之间的相关性。进行了细胞增殖、划痕愈合、transwell、流式细胞术、细胞周期、肿瘤球形成、免疫荧光（IF）、共免疫沉淀（co-IP）和染色质免疫沉淀（ChIP）实验，以进一步阐明 NCAPG2 在 PCa 中的分子机制。应用皮下和原位异种移植模型来研究 NCAPG2 在体内对 PCa 增殖的影响。串联质量标签（TMT）定量蛋白质组学用于检测 NCAPG2 过表达下的蛋白质组变化。
NCAPG2 在 PCa 中显著上调，其过表达与 PCa 进展和不良预后相关。NCAPG2 敲低抑制了 PCa 细胞的恶性行为，而其过表达则促进了 PCa 的侵袭性。NCAPG2 耗竭减弱了 PCa 在体内的发展和生长。TMT 定量蛋白质组学分析表明，c-MYC 活性与 NCAPG2 表达强烈相关。NCAPG2 在 PCa 中的促恶性作用是通过 c-MYC 介导的。NCAPG2 可以直接与 STAT3 结合，并诱导 STAT3 占据 MYC 启动子，从而转录激活 c-MYC 表达。最后，我们确定 NCAPG2 与癌症干细胞（CSC）标志物呈正相关，并增强了 PCa 细胞的自我更新能力。
NCAPG2 在 PCa 中高度表达，其水平与 PCa 预后显著相关。NCAPG2 通过 STAT3/c-MYC 信号通路促进 PCa 恶性程度并驱动癌症干性，这凸显了其作为 PCa 治疗靶点的潜力。
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