Abstract
BackgroundOvarian cancer (OC) is the gynecologic cancer with the highest mortality. Circular RNAs (circRNAs) play a vital role in the development and progression of cancer. This study aimed to explore the potential role of circ_0015756 in OC and its molecular mechanism.MethodsThe levels of circ_0015756, microRNA-942-5p (miR-942-5p) and Cullin 4B (CUL4B) were determined by quantitative real-time PCR (qRT-PCR) or Western blot assay. Cell proliferation, apoptosis, migration and invasion were assessed by Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry and transwell assay. The levels of proliferation-related and metastasis-related proteins were measured by Western blot assay. The relationship between miR-942-5p and circ_0015756 or CUL4B was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft assay was used to analyze tumor growth in vivo.ResultsCirc_0015756 and CUL4B levels were increased, while miR-942-5p level was decreased in OC tissues and cells. Depletion of circ_0015756 suppressed proliferation, migration and invasion and promoted apoptosis in OC cells. Down-regulation of circ_0015756 hindered OC cell progression via modulating miR-942-5p. Also, up-regulation of miR-942-5p impeded OC cell development by targeting CUL4B. Mechanistically, circ_0015756 up-regulated CUL4B via sponging miR-942-5p. Moreover, circ_0015756 silencing inhibited tumor growth in vivo.ConclusionKnockdown of circ_0015756 suppressed OC progression via regulating miR-942-5p/CUL4B axis, suggesting that circ_0015756 might be a potential therapeutic target for ovarian cancer.
Highlights
Ovarian cancer (OC) is a malignant tumor of the female reproductive system, and the mortality of epithelial OC ranks first among gynecological cancers [1]
Knockdown of circ_0015756 inhibits the proliferation, migration and invasion of OC cells and induces apoptosis To further explore the biological function circ_0015756 in OC, OV90 and SKOV3 cells were transfected with si-NC or si-circ_0015756
Cell Counting Kit-8 (CCK-8) and colony formation assays showed that circ_0015756 silencing suppressed the proliferation of OV90 and SKOV3 cells compared with the control group (Fig. 2b– d)
Summary
Ovarian cancer (OC) is a malignant tumor of the female reproductive system, and the mortality of epithelial OC ranks first among gynecological cancers [1]. Exploring the molecular mechanism of OC progression. Mounting evidence has corroborated that circRNAs with complex tissue specificity participate in tumorigenesis and development through multiple pathways [6]. Hsa_circ_0009910 facilitated the malignant behaviors of OC via down-regulating microRNA-145 [9]. Hsa_circRNA_102958 aggravated the progression of OC by regulating microRNA-1205/SH2D3A pathway [10]. A previous research revealed that hsa_circ_0015756 derived from complement factor H (CFH) was significantly up-regulated in OC tissues [11]. Circular RNAs (circRNAs) play a vital role in the development and progression of cancer. This study aimed to explore the potential role of circ_0015756 in OC and its molecular mechanism
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