Identification of circ_0038632 as a Promoter of Breast Cancer through miR-520a-3p-Dependent Modulation of CDCA3
Annals of clinical and laboratory science(2023)
Abstract
Objective. Emerging evidence proves the importance of circular RNAs (circRNAs) in many tumors, including breast cancer (BC). Here, we aimed to define a mechanism by which circ_0038632 regulates BC process. Methods. To quantify the expression of circ_0038632, miR-520a-3p and cell division cycle associated 3 (CDCA3), a quantitative real-time PCR or immunoblotting method was utilized. The relationships of circ_0038632/miR-520a-3p and miR-520a-3p/CDCA3 in BC cells were determined using RNA immunoprecipitation (RIP) experiment and luciferase reporter assay. The effects of the circ_0038632/ miR-520a-3p/CDCA3 cascade on cell biological phenotypes in vitro were examined by flow cytometry, EdU assay, cell counting kit 8 assay, transwell assay and wound healing assay. The function of circ_0038632 in tumorigenicity of BC cells in vivo was evaluated by xenograft experiments. Results. Circ_0038632 and CDCA3 were highly expressed and miR-520a-3p expression was hindered in human BC. Depletion of circ_0038632 weakened cell growth, motility, and invasiveness while promoted cell apoptosis. In terms of mechanism, miR-520a-3p targeted CDCA3, and circ_0038632 involved the post-transcriptional modulation of CDCA3 expression by working as a miR-520a-3p sponge. Silencing of miR-520a-3p could reverse the inhibitory functions of circ_0038632 depletion in BC cell malignant phenotypes. Re-expression of CDCA3 also overturned the suppressive effects of miR-520a-3p on BC cell malignant phenotypes. In addition, circ_0038632 depletion inhibited the growth of xenograft tumors in vivo. Conclusion. Taken together, circ_0038632 promotes breast carcinogenesis through the miR-520a-3p/CDCA3 regulatory cascade, indicating that circ_0038632 may be a potential target for BC treatment.
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Key words
Circ_0038632,breast cancer,miR-520a-3p,CDCA3
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