Department of Gynecology, The Fifth People's Hospital of Jinan, Jinan, China.
Department of Obstetrics, The Fifth People's Hospital of Jinan, Jinan, China.
Ann Med. 2023 Dec;55(1):908-919. doi: 10.1080/07853890.2023.2185289.
To explore the diagnostic value of circ-DENN domain containing 4 C (circDENND4C) in epithelial ovarian cancer (EOC) and the corresponding mechanism.
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.
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 .
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.
探讨环状 DENN 结构域包含 4C（circDENND4C）在卵巢上皮性癌（EOC）中的诊断价值及其相关机制。
采用 qRT-PCR 检测组织和血清标本以及 EOC 细胞系中 circDENND4C 和 miR-200b/c 的表达。从患者的临床记录中获取基本临床数据以及血清 HE4 和 CA125 水平。还评估了血清 circDENND4C 在 EOC 中的表达相关性和诊断价值。通过 CCK-8 和流式细胞术检测 circDENND4C 对细胞增殖和凋亡的影响。
EOC 组织中 circDENND4C 水平最低，miR-200b/c 水平最高，良性和正常组织次之。同样，EOC 患者血清 circDENND4C 最低，miR-200b/c 最高。此外，与健康女性相比，良性卵巢肿瘤患者的血清 circDENND4C 水平较低，而 miR-200b/c 的表达水平较高。circDENND4C 在 EOC 组织和血清标本中与 miR-200b/c 呈负相关，并且 EOC 患者的血清 circDENND4C 也与血清 HE4 和 CA125 呈负相关。circDENND4C 在组织和血清中的表达与 EOC 的 FIGO 和 TNM 分期以及肿瘤大小呈负相关。血清 circDENND4C 可将健康人与良性卵巢肿瘤和 EOC 患者区分开来，与血清 CA125 或 HE4 相比，其在 EOC 诊断中的特异性和准确性更高。circDENND4C 的上调通过下调 miR-200b/c 显著抑制 EOC 细胞增殖并促进细胞凋亡。
综上所述，circDENND4C 通过下调 miR-200b/c 在 EOC 中发挥肿瘤抑制作用，可能是 EOC 诊断的潜在肿瘤标志物。
在 EOC 组织或血清中，circDENND4C 表达最低，miR-200b/c 表达最高，良性和正常组织或血清中次之。
circDENND4C 参与 EOC 的恶性进展，具体而言，circDENND4C 的过表达通过下调 miR-200b/c 抑制 EOC 细胞增殖并刺激细胞凋亡，组织和血清中的 circDENND4C 表达与 EOC 的 FIGO 和 TNM 分期以及肿瘤大小密切相关。
与血清 CA125 或 HE4 相比，血清 circDENND4C 在 EOC 诊断中的特异性和准确性更高。
