Hsa_circ_0001445 works as a cancer suppressor via miR-576-5p/SFRP1 axis regulation in ovarian cancer

被引:11
作者
Wu, Yuhong [1 ,2 ,3 ]
Zhou, Jinhua [1 ]
Li, Yan [4 ]
Shi, Xiu [1 ]
Shen, Fangrong [1 ]
Chen, Mingwei [5 ]
Chen, Youguo [1 ]
Wang, Juan [1 ]
机构
[1] Soochow Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 899 Pinghai Rd, Suzhou 215006, Jiangsu, Peoples R China
[2] Soochow Univ, Jiangsu Key Lab Clin Immunol, Clin Res Ctr Obstet & Gynecol, Suzhou, Peoples R China
[3] Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Clin Immunol, Suzhou, Peoples R China
[4] First Peoples Hosp Yancheng, Dept Obstet & Gynecol, Suzhou, Peoples R China
[5] Anhui Med Univ, Affiliated Hosp 1, Dept Urol, Hefei, Peoples R China
关键词
ceRNA; hsa_circ_0001445; metastasis; miR-576-5p; ovarian cancer; SFRP1; CIRCULAR RNAS; CELL-PROLIFERATION; PROMOTES; EXPRESSION; DIAGNOSIS;
D O I
10.1002/cam4.5317
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Ovarian cancer (OC) has high mortality and morbidity. Circular RNA (circRNA) can deeply impact the tumor occurrence and growth. The pathogenic activity of one particular circRNA, hsa_circ_0001445 (hcR1445), in OC remains unclear and was therefore analyzed in this study. Methods Human OC tissue specimens and cell lines (SKOV3, HO8910, and OVCAR8) were used to examine the levels of hcR1445 and the microRNA miR-576-5p using polymerase chain reaction. The 5-ethynyl-2 '-deoxyuridine, flow cytometry, cellular scratch test, CCK-8, and Transwell migration assays were used to examine the biological activities of hcR1445 and miR-576-5p on cell apoptosis, invasion, migration, and proliferation in OC cells. Protein expression of WNT/beta-catenin and secreted frizzled-related protein 1 (SFRP1) were tested using Western blot analysis. The potential interactions of miR-576-5p/SFRP1 and hcR1445/miR-576-5p were evaluated using a dual-luciferase report assay. The effect of hcR1445 on OC growth and metastasis was further determined using an OC tumor xenograft model in vivo. Results hcR1445 level was declined in OC cells and tissues. hcR1445 reduced cellular invasion, proliferation, and migration by blocking the ability of miR-576-5p to upregulate SFRP1 expression and consequently prohibit WNT/beta-catenin signal transduction. hcR1445 upregulation suppressed OC growth, development, and intraperitoneal metastasis in vivo. Conclusion hcR1445 acts an antioncogene by targeting the miR-576-5p/SFRP1 axis and blocking OC progression and development. Thus, hcR1445 may be employed as an indicator or a possible therapeutic target in OC patients.
引用
收藏
页码:5736 / 5750
页数:15
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