Jinglong Liu1, Jian Zhang2, Zhifeng Wang3, Jingjing Xi4, Lixia Bai5, Yanxia Zhang6. 1. Department of Digestive, Shanxi Provincial People's Hospital, Taiyuan, China. 2. Intensive Care Unit, Hejin People's Hospital, Hejin, China. 3. Department of Digestive Endoscopy and Shanxi Provincial People's Hospital, Taiyuan, China. 4. Department of Oral Surgery, Shanxi Provincial People's Hospital, Taiyuan, China. 5. Department of Digestive, Yuanping First People's Hospital, Yuanping, China. 6. Inpatient Area III for Department of Gastroenterology, the Fifth People's Hospital of Datong, Datong, China.
Abstract
Background: Circular RNAs (circRNAs) have recently been reported to play essential roles in the progression of various cancers, including colorectal cancer (CRC). However, the roles of circRNA amyloid precursor-like protein 2 (circAPLP2) in CRC and its underlying mechanism have not been investigated. Materials and Methods: The expression levels of circAPLP2, microRNA-485-5p (miR-485-5p), and forkhead-box K1 (FOXK1) were determined by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide assay, flow cytometry, and transwell assay, respectively. Western blot assay was performed to measure the protein levels of proliferating cell nuclear antigen, Bcl-2, Bax, vimentin, E-cadherin, fibronectin, and FOXK1. The interaction between miR-485-5p and circAPLP2 or FOXK1 was predicted by starBase and verified by dual-luciferase reporter assay. A xenograft tumor model was established to confirm the functions of circAPLP2 in vivo. The lactate production was measured using lactate assay kit. Results: circAPLP2 expression was enhanced in CRC tissues and cells. circAPLP2 knockdown or miR-485-5p overexpression suppressed cell proliferation, migration, and invasion, whereas it promoted apoptosis in CRC cells, which was reversed by upregulating FOXK1. Moreover, miR-485-5p could directly bind to circAPLP2 and its downregulation reversed the suppressive effect of circAPLP2 knockdown on progression of CRC cells. In addition, FOXK1 was a downstream target of miR-485-5p. Furthermore, circAPLP2 modulated FOXK1 expression by sponging miR-485-5p in CRC cells. Besides, interference of circAPLP2 suppressed tumor growth in vivo and inhibited glycolysis in vitro by upregulating miR-485-5p and downregulating FOXK1. Conclusions: circAPLP2 knockdown inhibited CRC progression through regulating miR-485-5p/FOXK1 axis, providing a novel avenue for treatment of CRC.
Background: Circular RNAs (circRNAs) have recently been reported to play essential roles in the progression of various cancers, including colorectal cancer (CRC). However, the roles of circRNA amyloid precursor-like protein 2 (circAPLP2) in CRC and its underlying mechanism have not been investigated. Materials and Methods: The expression levels of circAPLP2, microRNA-485-5p (miR-485-5p), and forkhead-box K1 (FOXK1) were determined by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide assay, flow cytometry, and transwell assay, respectively. Western blot assay was performed to measure the protein levels of proliferating cell nuclear antigen, Bcl-2, Bax, vimentin, E-cadherin, fibronectin, and FOXK1. The interaction between miR-485-5p and circAPLP2 or FOXK1 was predicted by starBase and verified by dual-luciferase reporter assay. A xenograft tumor model was established to confirm the functions of circAPLP2 in vivo. The lactate production was measured using lactate assay kit. Results: circAPLP2 expression was enhanced in CRC tissues and cells. circAPLP2 knockdown or miR-485-5p overexpression suppressed cell proliferation, migration, and invasion, whereas it promoted apoptosis in CRC cells, which was reversed by upregulating FOXK1. Moreover, miR-485-5p could directly bind to circAPLP2 and its downregulation reversed the suppressive effect of circAPLP2 knockdown on progression of CRC cells. In addition, FOXK1 was a downstream target of miR-485-5p. Furthermore, circAPLP2 modulated FOXK1 expression by sponging miR-485-5p in CRC cells. Besides, interference of circAPLP2 suppressed tumor growth in vivo and inhibited glycolysis in vitro by upregulating miR-485-5p and downregulating FOXK1. Conclusions: circAPLP2 knockdown inhibited CRC progression through regulating miR-485-5p/FOXK1 axis, providing a novel avenue for treatment of CRC.