ABSTRACT
Objective@#Early detection and treatment are particularly important to epithelial ovarian cancer (EOC). Studies have shown that circular RNA (circRNA) dysregulation is associated with the proliferation and metastasis of ovarian cancer cells. This study focused on the role of serum exosomal circular forkhead box protein P1 (circFoxp1) on survival outcome and cisplatin (DDP) resistance in patients with EOC. @*Methods@#Quantitative polymerase chain reaction, 5-ethynyl-2′-deoxyuridine (EdU) staining, CCK-8, luciferase reporter assay, RNA immunoprecipitation, tumor xenograft in nude mice, and bioinformatic analysis were performed. @*Results@#Circulating exosomal circFoxp1 was significantly increased in patients with EOC, especially in DDP-resistant EOC patients. circFoxp1 expression was positively associated with International Federation of Gynecology and Obstetrics stage, primary tumor size, lymphatic metastasis, distant metastasis, residual tumor diameter, and clinical response. Exosomal circFoxp1 also was an independent factor predicting survival and disease recurrence in patients with EOC. Overexpression of circFoxp1 could promote cell proliferation and confer DDP resistance, while knockdown of circFoxp1 could inhibit cell proliferation and enhance DDP sensitivity in vitro and in vivo. In addition, miR-22 and miR-150-3p mimic treatment attenuated circFoxp1-meadiated DDP resistance, while miR-22 and miR-150-3p inhibitor treatment enhanced DDP resistance that mitigated by circFoxp1 knockdown. Furthermore, circFoxp1 positively regulated the expression of CCAAT enhancer binding protein gamma (CEBPG) and formin like 3 (FMNL3) through miR-22 and miR-150-3p. @*Conclusions@#circFoxp1 is an oncogene in EOC cells and can confer DDP resistance to EOC cells. Circulating exosomal circFoxp1 can be used as a biomarker and potential therapeutic target for EOC.
ABSTRACT
Objective@#Early detection and treatment are particularly important to epithelial ovarian cancer (EOC). Studies have shown that circular RNA (circRNA) dysregulation is associated with the proliferation and metastasis of ovarian cancer cells. This study focused on the role of serum exosomal circular forkhead box protein P1 (circFoxp1) on survival outcome and cisplatin (DDP) resistance in patients with EOC. @*Methods@#Quantitative polymerase chain reaction, 5-ethynyl-2′-deoxyuridine (EdU) staining, CCK-8, luciferase reporter assay, RNA immunoprecipitation, tumor xenograft in nude mice, and bioinformatic analysis were performed. @*Results@#Circulating exosomal circFoxp1 was significantly increased in patients with EOC, especially in DDP-resistant EOC patients. circFoxp1 expression was positively associated with International Federation of Gynecology and Obstetrics stage, primary tumor size, lymphatic metastasis, distant metastasis, residual tumor diameter, and clinical response. Exosomal circFoxp1 also was an independent factor predicting survival and disease recurrence in patients with EOC. Overexpression of circFoxp1 could promote cell proliferation and confer DDP resistance, while knockdown of circFoxp1 could inhibit cell proliferation and enhance DDP sensitivity in vitro and in vivo. In addition, miR-22 and miR-150-3p mimic treatment attenuated circFoxp1-meadiated DDP resistance, while miR-22 and miR-150-3p inhibitor treatment enhanced DDP resistance that mitigated by circFoxp1 knockdown. Furthermore, circFoxp1 positively regulated the expression of CCAAT enhancer binding protein gamma (CEBPG) and formin like 3 (FMNL3) through miR-22 and miR-150-3p. @*Conclusions@#circFoxp1 is an oncogene in EOC cells and can confer DDP resistance to EOC cells. Circulating exosomal circFoxp1 can be used as a biomarker and potential therapeutic target for EOC.
ABSTRACT
ObjectiveTo explore the possible mechanism of adult offspring rats'anxiety-like behavior induced by parents experienced morphine addiction and withdrawal.MethodsEstablishing the model of Sprague-Dawley rats morphine addiction,Male and female rats were mated after morphine withdrawal 21 days.Meaning-while,saline control group was established in the same method.5 female and 5 male offspring's brains were obtained to observe the neuronal morphology of hippocampal CA1 through Golgi staining when they were 8 weeks old,the same number of female and male's hippocampus were derived after deeply anesthetized to perform the whole genome expression profiles analysis.ResultsThe total length and the number of basal dendrites branches on hippocampal CA1 neurons in offspring of morphine groups were significantly decreased compared to the offspring of saline group.Comparison with the offspring of saline group,663 up-regulated genes (ratios ≥2.0) and 499 down-regulated genes ( ratios ≤0.5 ) were detected in the male offspring of morphine groups,and 350 up-regulated genes (ratios ≥2.0) and 188 down-regulated genes (ratios ≤0.5) were done in the female.Furthermore,they included many genes associated with regulation of emotional behavior,such as 5-HT2c receptor up-regulation 7-fold,Igf-2 up-regulation 7.1-fold and reelin down-regulation 3.3-fold were observed.ConclusionExperienced morphine addiction and withdrawal in parents prior to mating leads to dysplasia of dendritic morphology in hippocampal CA1 neurons of adult offspring rats,and 5-HT2c,Igf-2,reelin expressing abnormally,which may be the possible mechanism of anxiety-like behavior in adult offspring rats.