于君团队:PCID2或促进大肠癌
  • PCID2在原发性结直肠肿瘤中过表达,其高表达是预测CRC复发的独立因素;
  • PCID2在体外促进肿瘤细胞增殖与侵袭,在体内促进肿瘤形成与转移;
  • PCID2可促进细胞周期进程,抑制细胞凋亡;
  • PCID2和PML在CRC细胞中存在直接的物理作用和核共定位,PCID2通过促进PML的UPS介导的多泛素化增加其降解;
  • PCID2的致癌功能依赖于PML,PML竞争结合β连环蛋白,而PCID2通过降解PML抑制非典型Wnt信号,激活Wnt/β连环蛋白信号,同时抑制CTNNB1-ARF-P53轴。
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章台柳
全基因组测序显示,PCID2在结直肠癌中扩增。香港中文大学的于君团队在Oncogene发表文章,对结直肠癌中PCID2的表达、生物学功能、分子机制和临床特征进行研究,揭示了PCID2通过降解PML激活典型的Wnt/β连环蛋白信号,同时抑制CTNNB1-ARF-p53轴,发挥致癌功能,提示我们PCID2或可作为结直肠癌复发的独立预测标志物。
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Oncogene [IF:9.867]

A novel amplification gene PCI domain containing 2 (PCID2) promotes colorectal cancer through directly degrading a tumor suppressor promyelocytic leukemia (PML)

PCID2通过直接降解肿瘤抑制因子早幼粒细胞白血病蛋白基因(PML)促进结直肠癌

10.1038/s41388-021-01941-z

2021-10-08, Article

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Using whole genome sequencing, PCI Domain Containing 2 (PCID2) was identified to be amplified in colorectal cancer (CRC). In this study, we investigated the expression, biological function, molecular mechanism, and clinical implication of PCID2 in CRC. PCID2 mRNA and protein expression were higher in CRC cells and tumor tissues compared to healthy colonic tissues. The copy number of PCID2 was positively correlated with its mRNA expression. Multivariate analysis revealed that PCID2 is an independent prognostic factor for CRC recurrence. Functional studies showed that PCID2 promoted cell growth, cell cycle progression, and cell migration/invasion, while apoptosis was suppressed. Moreover, PCID2 promoted xenograft growth and lung metastasis in nude mice. Using co-immunoprecipitation and mass spectroscopy, we showed that PCID2 binds to promyelocytic leukemia (PML), a tumor suppressor involved in non-canonical β-catenin signaling. PCID2 promoted the degradation of PML via poly-ubiquitination, which in turn, induced Wnt/β-catenin signaling while simultaneously repressing ARF-p53 pathway. Thus, these results demonstrated that PCID2 functions as an oncogene in CRC by enhancing canonical Wnt/β-catenin signaling and inhibition of CTNNB1-ARF-p53 axis. PCID2 promoted canonical Wnt/β-catenin signaling in CRC via degradation of PML. PCID2 may serve as an independent prediction marker for CRC recurrence.

First Authors:
Jingwan Zhang,Jianning Zhai

Correspondence Authors:
Jun Yu

All Authors:
Jingwan Zhang,Jianning Zhai,Chi Chun Wong,Huarong Chen,Xiaohong Wang,Jiafu Ji,Jun Yu

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