CircATRNL1 and circZNF608 Inhibit Ovarian Cancer by Sequestering miR-152-5p and Encoding Protein

Abstract

Background: CircRNAs have been found to be involved in the pathogenesis of various diseases. We aimed to explore the roles of circRNAs in ovarian cancer.Methods: The expression levels of circRNAs in ovarian cancer and normal ovarian tissues were analyzed using RNA sequencing. Fluorescent in situ hybridization (FISH), proliferation assays and transwell assays were used to assess the effects of circRNAs on ovarian cancer.Results: CircATRNL1 and circZNF608 were downregulated in 20 ovarian cancer tissues compared to normal tissues. CircATRNL1 and circZNF608 are mainly located in the cytoplasm of ovarian cancer cells, and circATRNL1 is a highly conserved circRNA. The overexpression of circATRNL1 and circZNF608 inhibits the proliferation and invasion of ovarian cancer cells. We predicted miRNA–circRNA interactions for circZNF608 and circATRNL1 and obtained 63 interactions. However, a luciferase reporter assay showed that only miR-152-5p was sequestered by circZNF608. Bioinformatics analysis and experiments indicated that circATRNL1 contains an internal ribosome entry site and an open reading frame encoding a 131 aa protein.Conclusion: In conclusion, circATRNL1 and circZNF608 are two downregulated circRNAs in ovarian cancer and work as tumor suppressors. CircZNF608 may exert antitumor activity in ovarian cancer by binding miR-152-5p, and circATRNL1 may encode a 131 aa protein.

Prognostic Value of hsa_circ_0007615 in Epithelial Ovarian Cancer and its Regulatory Effect on Tumor Progression

“…Circ_0025033 has been denmonstrated to promote ovarian cancer development via regulating miR3703p/SLC1A5 axis [30]. Differentially expression of hsa_circ_0007615 was first indirectly reported by Lyu et al using RNA sequencing in ovarian cancer [31], implicating the role of hsa_circ_0007615 as a critical regulator in EOC. Our results demonstrate that hsa_circ_0007615 is frequently up-regulated in EOC compared to normal ovarian tissues or cells.…”

The role of circRNAs in regulation of drug resistance in ovarian cancer

“…Circ_0000554 was reported to increase cell invasion and proliferation via sponging miR-567 in ovarian cancer ( Wang et al, 2022b ). Both circATRNL1 and circZNF608 were found to suppress ovarian cancer progression via sequestering miR-152-5p and regulating encoding protein ( Lyu et al, 2022 ). CircCERS6 was revealed to inhibit tumor development via modulation of miR-630 and RASSF8 in epithelial ovarian cancer ( Li et al, 2022a ).…”

Circular RNAs in Epithelial Ovarian Cancer: From Biomarkers to Therapeutic Targets

“…In a mouse intraperitoneal xenograft model, overexpression of circATRNL1 significantly reduced the number and weight of tumor nodules in the abdomen, suggesting that circATRNL1 effectively represses tumor growth and metastasis in vivo. Additionally, Lyu et al [ 179 ] suggested that circATRNL1 may act as a tumor suppressor by encoding a 131 amino acid protein in EOC cells. CircATRNL1 was downregulated in tumor samples from stage III-IV HGSC patients, as compared with paired normal ovarian tissues, and it inhibited proliferation, migration, and invasion of EOC cells.…”