Tian Hao1, Yi Yang2, Juan He2, Jia Bai2, Yongjian Zheng1, Zhanpeng Luo3. 1. Department of Dermatology, Beijing Younger Medical Cosmetic Hospital, Beijing, PR China. 2. Department of Dermatology, The First Medical Center of Chinese PLA General Hospital, Beijing, PR China. 3. Department of Orthopedic, The 8th Medical Center of Chinese PLA General Hospital, Beijing, PR China. luozhanpeng_12@126.com.
Abstract
BACKGROUND: Although systemic therapies for melanoma have been improved, the 5-year survival rate of this aggressive cancer remains poor. It has been shown that hsa_circ_0062270 was upregulated in patients with melanoma. However, the relevant mechanism of hsa_circ_0062270 in the progression of melanoma remains unclear. METHODS: The CCK-8, EdU staining, flow cytometry, and transwell assays were used to determine the viability, proliferation, apoptosis and invasion in melanoma cells. An in vivo animal study was performed finally. RESULTS: The level of hsa_circ_0062270 was significantly upregulated in melanoma cells. In addition, hsa_circ_0062270 knockdown markedly inhibited the viability, proliferation, invasion and promoted the apoptosis of melanoma cells. Cell division cycle protein 45 (CDC45) is the host gene of hsa_circ_0062270, and downregulation of hsa_circ_0062270 notably decreased the expression of CDC45 in melanoma cells. Rescue assays confirmed that hsa_circ_0062270 regulated the growth of melanoma cells through CDC45. Moreover, RIP analysis showed that hsa_circ_0062270 interacted with RNA-binding protein (RBP) EIF4A3. Furthermore, in vivo study indicated that knockdown of hsa_circ_0062270 inhibited the melanoma tumor growth in vivo. CONCLUSIONS: Downregulation of hsa_circ_0062270 can inhibit the progression of melanoma through downregulation of CDC45. Our findings provide biological mechanisms for the use of hsa_circ_0062270 as a biomarker for melanoma and potential therapeutic target.
BACKGROUND: Although systemic therapies for melanoma have been improved, the 5-year survival rate of this aggressive cancer remains poor. It has been shown that hsa_circ_0062270 was upregulated in patients with melanoma. However, the relevant mechanism of hsa_circ_0062270 in the progression of melanoma remains unclear. METHODS: The CCK-8, EdU staining, flow cytometry, and transwell assays were used to determine the viability, proliferation, apoptosis and invasion in melanoma cells. An in vivo animal study was performed finally. RESULTS: The level of hsa_circ_0062270 was significantly upregulated in melanoma cells. In addition, hsa_circ_0062270 knockdown markedly inhibited the viability, proliferation, invasion and promoted the apoptosis of melanoma cells. Cell division cycle protein 45 (CDC45) is the host gene of hsa_circ_0062270, and downregulation of hsa_circ_0062270 notably decreased the expression of CDC45 in melanoma cells. Rescue assays confirmed that hsa_circ_0062270 regulated the growth of melanoma cells through CDC45. Moreover, RIP analysis showed that hsa_circ_0062270 interacted with RNA-binding protein (RBP) EIF4A3. Furthermore, in vivo study indicated that knockdown of hsa_circ_0062270 inhibited the melanoma tumor growth in vivo. CONCLUSIONS: Downregulation of hsa_circ_0062270 can inhibit the progression of melanoma through downregulation of CDC45. Our findings provide biological mechanisms for the use of hsa_circ_0062270 as a biomarker for melanoma and potential therapeutic target.
Authors: Jan Fiedler; Andrew H Baker; Stefanie Dimmeler; Stephane Heymans; Manuel Mayr; Thomas Thum Journal: Cardiovasc Res Date: 2018-08-01 Impact factor: 10.787