Ke Fang1, Xuan Chen2, Feng Qiu3, Jinbiao Xu1, Huanwen Xiong4, Zhanmin Zhang3. 1. Department of Oncology, High-Tech Hospital, First Affiliated Hospital of Nanchang University, Nanchang, China. 2. Department of Oncology, The Jiangxi Chest Hospital, Nanchang, China. 3. Department of Oncology, First Affiliated Hospital of Nanchang University, Nanchang, China. 4. Department of Respiratory, High-Tech Hospital, First Affiliated Hospital of Nanchang University, Nanchang, China.
Abstract
Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths all over the world. Exosomes exert central roles in intercellular communication. Circular RNA Rho GTPase activating protein 10 (circARHGAP10) was related to the development of NSCLC. Nevertheless, it was unclear whether circARHGAP10 can be mediated by serum-derived exosomes in NSCLC. Materials and Methods: Protein expression of CD63, CD81, family with sequence similarity 83F (FAM83F), glucose transporter 1 (Glut1), and lactate dehydrogenase were evaluated through Western blot analysis. The expression of circARHGAP10, miR-638, and FAM83F was examined by quantitative real-time polymerase chain reaction. Cell proliferation, migration, and invasion were evaluated through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) or transwell assays. Glucose consumption and lactate production were analyzed with special commercial kits. The relationship between circARHGAP10 or FAM83F and miR-638 was identified by dual-luciferase reporter or RNA immunoprecipitation (RIP) assays. The role of circARHGAP10 in vivo was confirmed through xenograft assay. Results: circARHGAP10 was upregulated in NSCLC tissues, cells, and serum-derived exosomes. Serum-derived exosomes boosted the expression of circARHGAP10 in NSCLC cells. circARHGAP10 depletion repressed proliferation, migration, invasion, and glycolysis of NSCLC cells in vitro, and curbed tumor growth in vivo. Also, miR-638 acted as a target of circARHGAP10, miR-638 overexpression overturned circARHGAP10 upregulation-mediated acceleration of proliferation, migration, invasion, and glycolysis of NSCLC cells. Besides, miR-638 targeted FAM83F and FAM83F overexpression abolished miR-638 enhancement-mediated proliferation, migration, invasion, and glycolysis of NSCLC cells. Conclusions: Inhibition of serum-derived exosomes-mediated circARHGAP10 curbed NSCLC progression through the miR-638/FAM83F axis.
Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths all over the world. Exosomes exert central roles in intercellular communication. Circular RNA Rho GTPase activating protein 10 (circARHGAP10) was related to the development of NSCLC. Nevertheless, it was unclear whether circARHGAP10 can be mediated by serum-derived exosomes in NSCLC. Materials and Methods: Protein expression of CD63, CD81, family with sequence similarity 83F (FAM83F), glucose transporter 1 (Glut1), and lactate dehydrogenase were evaluated through Western blot analysis. The expression of circARHGAP10, miR-638, and FAM83F was examined by quantitative real-time polymerase chain reaction. Cell proliferation, migration, and invasion were evaluated through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) or transwell assays. Glucose consumption and lactate production were analyzed with special commercial kits. The relationship between circARHGAP10 or FAM83F and miR-638 was identified by dual-luciferase reporter or RNA immunoprecipitation (RIP) assays. The role of circARHGAP10 in vivo was confirmed through xenograft assay. Results: circARHGAP10 was upregulated in NSCLC tissues, cells, and serum-derived exosomes. Serum-derived exosomes boosted the expression of circARHGAP10 in NSCLC cells. circARHGAP10 depletion repressed proliferation, migration, invasion, and glycolysis of NSCLC cells in vitro, and curbed tumor growth in vivo. Also, miR-638 acted as a target of circARHGAP10, miR-638 overexpression overturned circARHGAP10 upregulation-mediated acceleration of proliferation, migration, invasion, and glycolysis of NSCLC cells. Besides, miR-638 targeted FAM83F and FAM83F overexpression abolished miR-638 enhancement-mediated proliferation, migration, invasion, and glycolysis of NSCLC cells. Conclusions: Inhibition of serum-derived exosomes-mediated circARHGAP10 curbed NSCLC progression through the miR-638/FAM83F axis.