Circ_0015756 promotes the progression of ovarian cancer by regulating miR-942-5p/CUL4B pathway

Abstract

Background Ovarian 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. Methods The 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. Results Circ_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. Conclusion Knockdown 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.

CircRNAs as potent biomarkers in ovarian cancer: a systematic scoping review

“…Their function occurs through sponge of corresponding miRNAs. Circ-0015756 increases the progress of OC by sponging miR-942-5p and influencing the miR-942-5p/CUL4B axis [88]. Similarly, the circ-0002711/miR-1244/ ROCK1 and has-circ-0015326/miR-127-3p/MYB pathways are key players in OC with potential as therapeutic targets [89,90].…”

“…Numerous studies have shown that circ-0015756, circ-0002711, hsa-circ-0015326, circ-0001068, circ-0025033 and circ-KIF4A are oncogenic circRNAs with diagnostic and prognostic value in OC [88][89][90][91][92][93][94]. Their function occurs through sponge of corresponding miRNAs.…”

miR‐942‐5p prevents sepsis‐induced acute lung injury via targeting TRIM37

“…miR-942-5p has been found to have diverse biological functions in several diseases. For instance, miR-942-5p has been reported as an anti-oncogene in ovarian cancer 6 and oral squamous cell carcinoma. [10][11][12][13] In addition, Wang et al revealed that miR-942-5p was involved in the regulatory roles of lncRNA SOX2-OT on doxorubicin-induced cardiomyocyte apoptosis.…”

“…3,4 When ALI occurs, the injury to alveolar epithelial cells caused by lipopolysaccharide (LPS) may lead to endothelial barrier dysfunction. [5][6][7][8] Therefore, it is of potential clinical importance to protect the damaged alveolar epithelial cells from sepsis-induced ALI.…”

“…[10][11][12][13]19 In recent years, several lines of evidence suggest the pivotal roles of miRNA in sepsis, such as miR-223, 20 miR-133a 21,22 and miR-186. 23,24 miRNA-942-5p is shown to be involved in many cellular processes, such as tumour cell phenotypes, 6,12,23,24 osteogenic differentiation, 25,26 cardiomyocyte apoptosis, 27 and the oxidative stress and inflammatory response of vascular endothelial cells. 28 More importantly, a recent report implies that miR-942-5p expression is downregulated in LPS-induced HK-2 cells, and participates in inflammation and cell apoptosis, suggesting that miR-942-5p might be involved in sepsis-induced acute kidney injury (AKI).…”