OncoTargets and Therapy (Apr 2019)
Nr5a2 promotes tumor growth and metastasis of gastric cancer AGS cells by Wnt/beta-catenin signaling
Abstract
Lei Liu,1–3 Yan Li,4 Biran Pan,1–3 Tongtong Zhang,1–3 Danfeng Wei,1–3 Yifang Zhu,1–3 Yuanbiao Guo1–31Medical Research Center, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of China; 2The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, People’s Republic of China; 3The Second Chengdu Hospital Affiliated to Chongqing Medical University, Chengdu, Sichuan, People’s Republic of China; 4Department of General Surgery, No. 42 Hospital of PLA, Leshan, Sichuan, People’s Republic of ChinaPurpose: Nr5a2 (nuclear receptor subfamily 5 group A member 2, also known as LRH-1), which belongs to the NR5A (Ftz-F1) subfamily of nuclear receptors, is a key regulator in stem cell pluripotency and the development of several types of cancer. However, the data are controversial. Since Nr5a2 plays different roles in multiple types of cancer and the function of Nr5a2 in gastric cancer (GC) has not been revealed, we studied the role and molecular mechanism of Nr5a2 in GC.Methods: In this study, we have investigated the effect of Nr5a2 on tumor growth and metastasis by in vivo and in vitro models.Results: The results showed that knockdown of Nr5a2 could inhibit cell proliferation via arresting the cell cycle in the G2/M phase and suppress cell mobility through preventing the epithelial-mesenchymal transition (EMT) process in AGS cells. In addition, knockdown of Nr5a2 could suppress tumorigenesis and metastasis of AGS cells in vivo. We also demonstrated that knockdown of Nr5a2 inhibited cellular proliferation and mobility by suppressing the Wnt/beta-catenin signaling pathway.Conclusion: Nr5a2 may act as an oncogene in GC development. The EMT process and the Wnt/beta-catenin signaling pathway play an important role in the Nr5a2 induced GC development.Keywords: Nr5a2, gastric cancer, proliferation, metastasis, Wnt/beta-catenin
