Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Cell Signal. 2023 Oct;110:110844. doi: 10.1016/j.cellsig.2023.110844. Epub 2023 Aug 6.
Non-SMC condensin II complex subunit G2 (NCAPG2) is one of the three non-SMC subunits in condensin II, which plays a vital role in regulating chromosome condensation and segregation. Although the tumor-promoting role of NCAPG2 has been reported in several solid malignancies, its function in breast invasive carcinoma (BRCA) remains unknown. Data both from GEPIA and GSE36295 indicated that NCAPG2 mRNA expression was abnormally upregulated in cancer tissues, which was further verified in 40 paired BRCA and para-carcinoma samples. Kaplan-Meier Plotter further illustrated that BRCA patients with higher NCAPG2 expression have a poorer prognosis. Functional experiments carried out in two BRCA cell lines (MCF-7 and T-47D) showed that NCAPG2-silenced BRCA cells acquired less aggressive behavior - weakened growth and metastasis both in vitro and in vivo. Label-free proteomics quantified the protein expression patterns in MCF-7 cells, and the results revealed 684 differentially expressed proteins (|logFC| > 1 and P < 0.05) downstream to NCAPG2. Interestingly, poly(C)-binding protein 2 (PCBP2), an RNA binding protein previously known to increase RNA stability of its target genes, was found to directly bind to and protect NCAPG2 mRNA from degradation-PCBP2 knockdown accelerated the degradation half-life time of NCAPG2 mRNA from approximately 8 h to 5 h. Taken together, our study indicates that NCAPG2 acts as a novel contributor to BRCA growth and metastasis under the regulation of PCBP2, providing insights into BRCA treatment.
非 SMC 凝聚素 II 复合物亚基 G2（NCAPG2）是非 SMC 凝聚素 II 中的三个非 SMC 亚基之一，在调节染色体浓缩和分离中起着至关重要的作用。尽管 NCAPG2 在几种实体恶性肿瘤中具有促进肿瘤的作用，但它在乳腺浸润性癌（BRCA）中的功能尚不清楚。来自 GEPIA 和 GSE36295 的数据均表明，NCAPG2mRNA 在癌症组织中异常上调，在 40 对 BRCA 和癌旁样本中得到了进一步验证。Kaplan-Meier Plotter 进一步表明，NCAPG2 表达较高的 BRCA 患者预后较差。在两种 BRCA 细胞系（MCF-7 和 T-47D）中进行的功能实验表明，沉默 NCAPG2 的 BRCA 细胞获得了侵袭性较弱的行为-体外和体内的生长和转移能力均减弱。无标记蛋白质组学定量分析 MCF-7 细胞中的蛋白质表达模式，结果显示 NCAPG2 下游有 684 种差异表达蛋白（|logFC|>1 和 P<0.05）。有趣的是，先前已知可增加其靶基因 RNA 稳定性的多聚（C）结合蛋白 2（PCBP2）被发现可直接结合并保护 NCAPG2mRNA 免受降解-PCBP2 敲低可将 NCAPG2mRNA 的降解半衰期从大约 8 小时加速至 5 小时。总之，我们的研究表明，NCAPG2 在 PCBP2 的调节下作为 BRCA 生长和转移的新贡献者发挥作用，为 BRCA 的治疗提供了新的见解。
