Abstract
Recent studies have shown that the expression of ENPP1 is related to differentiation, death, dissemination and chemosensitivity of tumor cells. So far, there is no research in ovarian carcinoma. This study aimed at exploring the role of ENPP1 gene in ovarian carcinoma, the relationship with prognostic indicators and chemotherapy resistance, and investigates the possibility of molecular targeted therapy. The expression of ENPP1 in 41 normal ovarian epithelial tissues, 97 ovarian serous cystadenoma and 103 HGSOC tissues was detected by IHC. In ovarian cancer tissues and ovarian cancer cell lines, mRNA and protein expression of ENPP1 was determined by qRT-PCR and Western blot. The ENPP1 expression was knockdowned by siRNA. Cell proliferation was measured with the BrdU Cell Proliferation ELISA. Cell migration and invasion were detected by Wound-Healing, Transwell migration and Matrigel invasion assay. Caspase 3 activity was determined by the CaspACE. The expression of EMT markers such as E-cadherin, N-cadherin, and Vimentin was measured, and the expression of PCNA and MMP9 was also be detected. The results showed that the expression of ENPP1 was significantly increased in high-grade ovarian serous carcinoma, the number of strong expression was 85.4% (22.3%+63.1%) and only 1.03% (1.03%+0.0%) in serous cystadenoma, but no in normal ovarian epithelium (P< 0.05). And the stronger the expression of ENPP1, the later the FIGO stage and the poorer differentiation of cells (P = 0.001 or <0.001, respectively). However, no correlation was found between the expression of ENPP1 and chemosensitivity. ENPP1 was also highly expressed in ovarian cancer tissues and in epithelial ovarian cancer cell lines (A2780, CaoV3, OVCAR3, SKOV3 and 3ao). After down-regulation of ENPP1 expression by RNA interference, the cell proliferation, migration and invasion of ovarian cancer cell decreased significantly, the expression of apoptosis related gene caspase 3 increased significantly, while the expression of PCNA and MMP9 was significantly down regulated. In addition, EMT biological characteristics of A2780 and SKOV3 cells were also inhibited. In summary, the increased expression of ENPP1 may be related to the occurrence of HGSOC, and indicate that the disease progresses rapidly and the prognosis is poor. ENPP1 may be considered as a potential molecular therapeutic target.
Highlights
Almost 240,000 women worldwide are diagnosed with ovarian cancer every year
QRT-PCR results showed that the expression of Ecto-nucieotdepyrophosphatase/ phosphodesterasel (ENPP1) mRNA in high grade serous ovarian carcinoma (HGSOC) was significantly higher than that in normal ovarian tissue and ovarian serous cystadenoma (t = 18.423, P = 0.000)
We found that the ENPP1 mRNA expression was down regulated by 85.47% after transfection with PC-1 siRNA
Summary
Almost 240,000 women worldwide are diagnosed with ovarian cancer every year. The incidence of ovarian cancer ranks second in female malignant tumors, the total mortality rate is almost three times that of breast cancer, making it the most lethal gynecological malignancy in developed countries. Because there are no early clinical symptoms and signs, and there is no effective method for early screening and diagnosis, about 70% of patients have been diagnosed in advanced stage, and the prognosis is generally poor. The 5-year survival rate of patients with stage III or IV was less than 25% [1, 2]. The mortality rate has ranked to first in female tumors, and the incidence rate has a younger trend in recent years [4,5,6]
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