Abstract
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.
Highlights
Cervical cancer (CC) typically occurs in the cervix as squamous cell carcinomas, largely resulted from sustained infections with human papillomavirus (HPV) [1,2,3]
We examined the mRNA levels of Pituitary Tumor Transforming Gene 1 (PTTG1) and PTTG3P in 10 CC specimens, compared to the paired adjacent normal cervical tissue (NCT) by reverse transcription and quantitative RT-PCR (RT-qPCR) (Figure 1AB)
We found that compared to NCT, CC tissue had a significantly higher level of PTTG1 (Figure 1A), and a significantly higher level of PTTG3P (Figure 1B)
Summary
Cervical cancer (CC) typically occurs in the cervix as squamous cell carcinomas, largely resulted from sustained infections with human papillomavirus (HPV) [1,2,3]. The malignancy of CC is mainly contributable to its outgrowth and metastasis, which leads to a compelling requirement for a full comprehension of the molecular mechanisms controlling CC growth and invasiveness [1]. Pituitary Tumor Transforming Gene 1 (PTTG1) is a potent cell-cycle activator [4]. It is a critical substrate that joins to an anaphase-promoting complex (APC) with separin to lead to the APC activation [4]. PTTG1 is highly expressed in many different types of tumors, and enhances tumor cell growth and metastasis through complicated while not-fully-determined mechanisms [511]
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