Guo Xiang-Cui, Li Li, Gao Zhi-Hui, Zhou Hong-Wei, Li Jun, Wang Qian-Qing
Gynecologic Oncology, Xinxiang City Central Hospital, Xinxian 453000, Henan, China.
Nuclear Medicine Department, Xinxiang City Central Hospital, Xinxian 453000, Henan, China.
Aging (Albany NY). 2019 Mar 10;11(5):1333-1341. doi: 10.18632/aging.101830.
The outgrowth and metastasis of cervical cancer (CC) contribute to its malignancy. Pituitary Tumor Transforming Gene 1 (PTTG1) is upregulated in many types of cancer, and enhances tumor cell growth and metastasis. However, the activation and regulation of PTTG1 in CC, especially by its pseudogene PTTG3P, have not been shown. Here, we detected significantly higher levels of PTTG1 and PTTG3P in the resected CC tissue, compared to the paired adjacent normal cervical tissue. Interestingly, the PTTG3P levels positively correlated with the PTTG1 levels. High PTTG3P levels were associated with poor patients' survival. In vitro, PTTG1 were increased by PTTG3P overexpression, but was inhibited by PTTG3P depletion in CC cells. However, PTTG3P levels were not altered by modulation of PTTG1 in CC cells, suggesting that PTTG3P is upstream of PTTG1. Moreover, PTTG3P increased CC cell growth, likely through CCNB1-mediated increase in cell proliferation, rather than through decrease in cell apoptosis. Furthermore, PTTG3P increased CC cell invasiveness, likely through upregulation of SNAIL and downregulation of E-cadherin. Our work thus suggests that PTTG3P may promote growth and metastasis of CC through PTTG1.
宫颈癌（CC）的生长和转移促成了其恶性特征。垂体肿瘤转化基因1（PTTG1）在多种癌症中表达上调，并促进肿瘤细胞的生长和转移。然而，CC中PTTG1的激活和调控，尤其是通过其假基因PTTG3P的调控，尚未见报道。在此，我们检测到与配对的相邻正常宫颈组织相比，切除的CC组织中PTTG1和PTTG3P水平显著更高。有趣的是，PTTG3P水平与PTTG1水平呈正相关。PTTG3P水平高与患者生存率低相关。在体外，CC细胞中PTTG3P过表达可增加PTTG1水平，而PTTG3P缺失则抑制PTTG1水平。然而，CC细胞中PTTG1的调节并未改变PTTG3P水平，这表明PTTG3P在PTTG1的上游。此外，PTTG3P可能通过CCNB1介导的细胞增殖增加而非细胞凋亡减少来促进CC细胞生长。此外，PTTG3P可能通过上调SNAIL和下调E-钙黏蛋白来增加CC细胞的侵袭性。因此，我们的研究表明PTTG3P可能通过PTTG1促进CC的生长和转移。
