circDENND4C, a novel serum marker for epithelial ovarian cancer, acts as a tumor suppressor by downregulating miR-200b/c

Research objective: To explore the diagnostic value of circ-DENN domain containing 4 C (circDENND4C) in epithelial ovarian cancer (EOC) and the corresponding mechanism.

Methods: We determined the expression of circDENND4C and miR-200b/c in tissues and serum specimens as well as EOC cell lines using qRT-PCR. Basic clinical data, and serum HE4 and CAl25 levels were acquired from patients' clinical records. Expression-related correlations and the diagnostic value of serum circDENND4C in EOC were also estimated. CCK-8 and flow cytometry were performed to detect the effect of circDENND4C on cell proliferation and apoptosis.

Results: circDENND4C level was lowest while miR-200b/c was highest in EOC tissues, followed by benign and normal tissues. Similarly, serum circDENND4C was lowest while miR-200b/c was highest in EOC patients. Moreover, serum circDENND4C was lower in patients with benign ovarian tumors than in healthy women, while miR-200b/c expression was higher. circDENND4C was negatively associated with miR-200b/c in EOC tissues and serum specimens, and serum circDENND4C was also negatively correlated with serum HE4 and CAl25 in EOC patients. circDENND4C expression in both tissue and serum was negatively related to FIGO and TNM stage, and tumor size in EOC. Serum circDENND4C could distinguish healthy persons from patients with benign ovarian tumors and EOC, and they showed a higher specificity and accuracy than serum CA125 or HE4 in EOC diagnosis. circDENND4C upregulation significantly suppressed EOC cell proliferation and facilitated apoptosis by downregulating miR-200b/c in vitro.

Conclusions: Summarily, circDENND4C acts as a tumor inhibitor by downregulating miR-200b/c in EOC and could be a possible tumor marker for EOC diagnosis.KEY MESSAGEScircDENND4C expression was lowest while miR-200b/c was highest in EOC tissues or serums, followed by benign and normal tissues or serums.circDENND4C was involved in malignant progression of EOC, concretely, overexpression of circDENND4C suppressed EOC cell proliferation and stimulated apoptosis via downregulating miR-200b/c, and circDENND4C expression in both tissue and serum was closely related to FIGO and TNM stages and tumor size in EOC.Serum circDENND4C showed a higher specificity and accuracy than serum CA125 or HE4 in EOC diagnosis.HIGHLIGHTScircDENND4C expression was lowest while miR-200b/c was highest in EOC tissues, followed by benign and normal tissues.Serum circDENND4C was lowest while miR-200b/c was highest in EOC patients, followed by benign patients and healthy women.Overexpression of circDENND4C suppresses EOC cell proliferation and stimulates apoptosis via downregulating miR-200b/c.circDENND4C expression in both tissue and serum was closely related to FIGO and TNM stage and tumor size in EOC.Serum circDENND4C showed a higher specificity and accuracy than serum CA125 or HE4 in EOC diagnosis.