OncoTargets and Therapy (Nov 2020)
RHPN2 Promotes Malignant Cell Behaviours in Ovarian Cancer by Activating STAT3 Signalling
Abstract
Fengsheng Yu,1 Pingping Qiao,2 Guangjie Yin,1 Yewu Sun,1 Xiao Yu,1 Xin Sun,1 Yijing Chu,1 Yankui Wang1 1Department of Gynaecology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Neurology, The Third People’s Hospital of Qingdao, Qingdao, People’s Republic of ChinaCorrespondence: Yankui Wang; Yijing ChuDepartment of Gynaecology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266061, People’s Republic of ChinaTel +86-18661808529; +86-17853297008Email [email protected]; [email protected]: Ovarian cancer is the fifth most common cause of cancer-related deaths and accounts for 3% of cancer cases occurring in women. Therefore, determining the underlying genes that can promote ovarian cancer progression is of great urgency. It has been reported that RHPN2 promotes tumour progression in various types of cancer, but its role in ovarian cancer pathogenesis remains unknown.Materials and Methods: In this study, bioinformatic datasets were used to predict the expression of RHPN2 in clinical samples and determine the relationship between RHPN2 and the prognosis of ovarian cancer patients. Clinical samples were used to verify the prediction. RHPN2-targeting shRNA was used to investigate the effect of RHPN2 on ovarian cancer cells, and following RHPN2 knockdown, the proliferative and migratory capacities of ovarian cancer cells were tested. To determine the downstream signalling target of RHPN2, a luciferase reporter assay was conducted, and an animal experiment was carried out to confirm the effect of RHPN2 in vivo.Results: The public datasets indicated that ovarian cancer tissues showed significantly higher RHPN2 expression than para-cancer normal tissues, and poor prognosis was observed in patients with higher RHPN2 expression, which was further confirmed in clinical samples. After RHPN2 was knocked down, the proliferation and migration of ovarian cancer cells were significantly impaired; a luciferase reporter assay indicated that the STAT3 signalling pathway was the most highly affected, and RHPN2 downregulation inhibited STAT3 nuclear translocation. STAT3 inhibitors partially rescued the tumour-promoting effect induced by RHPN2 overexpression, which was further confirmed by animal experiments.Conclusion: Collectively, our results indicate that RHPN2 promotes malignant behaviours in ovarian cancer by activating STAT3 signalling.Keywords: ovarian cancer, STAT3, RHPN2
