Wenjie Hou1, Yueming Zhang2. 1. Department of Gynecology and Obstetrics, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China. 2. Department of Gynecology and Obstetrics, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China. Electronic address: lionhoumail@163.com.
Abstract
BACKGROUND: Ovarian cancer (OC) is the leading disorder to threaten women's lives. Numerous circular RNAs (circRNAs) were identified in cancers with dysregulation and involved in the pathogenesis of cancer. This study investigated the function and regulatory mechanism of circ_0025033 in OC development, aiming to provide a potential strategy for OC treatment. METHODS: For expression analysis, the expression levels of circ_0025033, LSM4 mRNA and miR-184 were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein level of LSM4 expression was detected by western blot. For functional analysis, the capacities of colony formation, migration/invasion and glycolysis metabolism were assessed by colony formation assay, transwell assay and the levels of glucose consumption and lactate production. The interaction between miR-184 and circ_0025033 or LSM4 was predicted by the bioinformatics tool and validated by dual-luciferase reporter assay. Xenograft models were established to determine the role of circ_0025033 in vivo. RESULTS: The expression of circ_0025033 and LSM4 was promoted in OC tissues and cells. Circ_0025033 knockdown or LSM4 knockdown blocked the ability of colony formation, migration/invasion and glycolysis metabolism in OC cells. In mechanism, circ_0025033 functioned as a "competing endogenous RNA (ceRNA)" to modulate LSM4 expression by targeting miR-184. LSM4 overexpression recovered the inhibitory effects on colony formation, migration/invasion and glycolysis metabolism caused by circ_0025033 knockdown. Moreover, circ_0025033 knockdown also inhibited tumor growth in vivo by regulating LSM4 and targeting miR-184. CONCLUSION: Circ_0025033 promotes the progression of OC by regulating LSM4 expression via targeting miR-184, which provided a new strategy to treat OC.
BACKGROUND:Ovarian cancer (OC) is the leading disorder to threaten women's lives. Numerous circular RNAs (circRNAs) were identified in cancers with dysregulation and involved in the pathogenesis of cancer. This study investigated the function and regulatory mechanism of circ_0025033 in OC development, aiming to provide a potential strategy for OC treatment. METHODS: For expression analysis, the expression levels of circ_0025033, LSM4 mRNA and miR-184 were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein level of LSM4 expression was detected by western blot. For functional analysis, the capacities of colony formation, migration/invasion and glycolysis metabolism were assessed by colony formation assay, transwell assay and the levels of glucose consumption and lactate production. The interaction between miR-184 and circ_0025033 or LSM4 was predicted by the bioinformatics tool and validated by dual-luciferase reporter assay. Xenograft models were established to determine the role of circ_0025033 in vivo. RESULTS: The expression of circ_0025033 and LSM4 was promoted in OC tissues and cells. Circ_0025033 knockdown or LSM4 knockdown blocked the ability of colony formation, migration/invasion and glycolysis metabolism in OC cells. In mechanism, circ_0025033 functioned as a "competing endogenous RNA (ceRNA)" to modulate LSM4 expression by targeting miR-184. LSM4 overexpression recovered the inhibitory effects on colony formation, migration/invasion and glycolysis metabolism caused by circ_0025033 knockdown. Moreover, circ_0025033 knockdown also inhibited tumor growth in vivo by regulating LSM4 and targeting miR-184. CONCLUSION: Circ_0025033 promotes the progression of OC by regulating LSM4 expression via targeting miR-184, which provided a new strategy to treat OC.