Knockdown of NRSF inhibits cell proliferation of ovarian cancer via activating Hippo pathway

Abstract

AimsOvarian cancer is the most leading cause of deaths among gynecologic malignancies, and Neuron-restrictive silencer factor (NRSF) can be upregulated or downregulated according to the type of tumor. However, the expression and function of NRSF in ovarian cancer is still unknown. Main methodsExpression of NRSF in normal ovary and ovarian cancer cells were evaluated by quantitative PCR (qPCR). NRSF expression in normal ovary and ovarian cancer tissue samples were examined by qPCR, western blotting and immunohistochemistry (IHC). MTT, colony formation, anchorage-independent growth assay were applied to examine the effect of NRSF on ovarian cancer cell proliferation. Bromodeoxyuridine (BrdUrd) labeling and flow cytometry assay were carried out to investigate the role of NRSF on cell cycle of ovarian cancer cells. Luciferase reporter assay and western blotting, immunofluorescence labeling were devoted to explore the mechanism by which NRSF contributes to proliferation of ovarian cancer cells. Key findingsThe results demonstrated that NRSF is significantly upregulated in ovarian cancer cells and tissues and negatively related with the survival of patients with ovarian cancer, and knockout of NRSF inhibit proliferation of ovarian cancer cells. Further analysis showed that NRSF can influence G1/S transition of cell cycle via regulating the transcription of Hippo pathway. SignificanceHerein, our study suggest that NRSF is associated with the progression of ovarian cancer, and NRSF may be a valuable early detection marker of ovarian cancer and inhibiting NRSF expression may be an effective method to treat ovarian cancer.