MiR-760 overexpression promotes proliferation in ovarian cancer by downregulation of PHLPP2 expression.

OBJECTIVE: Ovarian cancer is one of the most lethal gynecologic malignancies worldwide and with poor prognosis and survival rate in women. Identifying sensitive and specific molecular in carcinogenesis may improve diagnostic and therapeutic strategies for this malignancy and achieve a better clinical outcome. METHODS: miR-760 expression in ovarian cancer cell lines and patient tissues were determined using Real-time PCR. 145 human ovarian cancer tissue samples were analyzed by RT-PCR to investigate the association between miR-760expression and the clinicopathological characteristics of ovarian cancer patients. Functional assays, such as MTT, anchorage-independent growth, colony formation and BRDU assay were used to determine the oncogenic role of miR-760 in human ovarian cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of miR-760 promotes proliferation in ovarian cancer cells. RESULT: The expression of miR-760 was markedly upregulated in ovarian cancer cell lines and tissues, and high miR-760 expression was associated with an aggressive phenotype and poor prognosis with ovarian cancer patients. Upregulation of miR-760 promoted, whereas downregulation of miR-760 inhibited the proliferation of ovarian cancer cells in vitro. Additionally, we identified PHLPP2 as a direct target of miR-760, and silencing the expression of PHLPP2 is the essential biological function of miR-760 during ovarian cancer cell proliferation. Finally, we showed a significant correlation between miR-760 and PHLPP2 expression in ovarian cancer tissues. CONCLUSION: Our findings suggest that miR-760 represents a potential onco-miR and participates in ovarian cancer carcinogenesis, which highlight its potential as a target for ovarian cancer therapy.

CREB5 promotes tumor cell invasion and correlates with poor prognosis in epithelial ovarian cancer.

CAMP responsive element binding protein 5 (CREB5) has crucial roles in regulating cell growth, proliferation, differentiation and cell cycle regulation. CREB5 has been identified to be overexpressed in several types of human cancer. However, the expression characteristics of CREB5 in epithelial ovarian cancer remains unknown, and its potential clinical prognostic significance has not yet been elucidated. In the present study, quantitative polymerase chain reaction (qPCR) and western blot analysis were performed to detect CREB5 mRNA and protein expression levels in 10 fresh tissue and cell lines epithelial ovarian cancer. Furthermore, CREB5 expression was analyzed using immunohistochemical analysis in 125 clinicopathologically characterized ovarian cancers: Stage I+II (n=31), stage III (n=70), stage IV (n=24). The patient survival rate was evaluated using Kaplan-Meier analysis. CREB5 was significantly overexpressed at both the mRNA and protein levels in epithelial ovarian cancer cells. There was a significant positive correlation between high CREB5 expression and increasing the International Federation of Gynecology and Obstetrics (FIGO) stage and pelvic lymph node metastasis (P<0.05). Patients with high CREB5 expression had a shorter overall survival, whereas patients with low CREB5 expression had longer survival. In addition, patients with high CREB5 expression had shorter relapse-free survival whereas patients with low CREB5 expression had longer relapse-free survival. Univariate logistic regression analysis and stepwise multivariate analysis all revealed that the FIGO stage and high CREB5 expression were significant risk factors for epithelial ovarian cancer (P<0.001), which suggested that CREB5 upregulation may be associated with a poor prognosis; therefore, it may be an independent prognostic indicator of epithelial ovarian cancer and may serve as a tumor-aggressive gene.