PDF(Pubmed)
Abstract：
UNASSIGNED: A growing corpus of research has revealed that circular RNAs (circRNAs) have become increasingly important for the growth of malignancies in recent years. CircRNAs as ideal candidates for breast cancer (BC) therapeutic targets is still absent.
UNASSIGNED: In our study, the dysregulated circRNAs in BC progression were explored, we analysed the BC\'s circRNA expression profiles using publicly available datasets (GSE101124 and GSE101122). The expression of circZEB1 in BC and cell lines was investigated by qPCR. RNase and actinomycin D were used to examine the features of circZEB1. The function of circZEB1 was subsequently investigated through the utilisation of colony formation, tube formation, transwell assays, and xenograft animal models.RNA immunoprecipitation (RIP), luciferase reporter assays, immunoprecipitation (co-IP) test in conjunction with LC-MS, and ChIP-seq assay to investigate the molecular mechanism underlying the biological activity of circZEB1 in BC.
UNASSIGNED: Among the circRNAs, we were particularly interested in hsa_circ_0000228, which is spliced from the oncogene ZEB1. In BC cell lines, CircZEB1 expression was upregulated. CircZEB1 knockdown prevented BC cells from migrating and invading, as well as HUVECs from forming tubes and developing. By sponging miR-337-3p, functional testing revealed that circZEB1 promoted O-GlcNAcylation, increased YBX1, and OGT expression. Moreover, circZEB1 overexpression is reversible, in contrast to YBX1 knockdown, which mostly results in the downregulation of multiple oncogenes.
UNASSIGNED: Our study indicate that circZEB1 had oncogenic function in BC by focusing on circZEB1/miR-337-3p/OGT and YBX1. It might be inferred that circZEB1 could be a promising new target for BC treatment.
UNASSIGNED: In our study, the dysregulated circRNAs in BC progression were explored, we analysed the BC\'s circRNA expression profiles using publicly available datasets (GSE101124 and GSE101122). The expression of circZEB1 in BC and cell lines was investigated by qPCR. RNase and actinomycin D were used to examine the features of circZEB1. The function of circZEB1 was subsequently investigated through the utilisation of colony formation, tube formation, transwell assays, and xenograft animal models.RNA immunoprecipitation (RIP), luciferase reporter assays, immunoprecipitation (co-IP) test in conjunction with LC-MS, and ChIP-seq assay to investigate the molecular mechanism underlying the biological activity of circZEB1 in BC.
UNASSIGNED: Among the circRNAs, we were particularly interested in hsa_circ_0000228, which is spliced from the oncogene ZEB1. In BC cell lines, CircZEB1 expression was upregulated. CircZEB1 knockdown prevented BC cells from migrating and invading, as well as HUVECs from forming tubes and developing. By sponging miR-337-3p, functional testing revealed that circZEB1 promoted O-GlcNAcylation, increased YBX1, and OGT expression. Moreover, circZEB1 overexpression is reversible, in contrast to YBX1 knockdown, which mostly results in the downregulation of multiple oncogenes.
UNASSIGNED: Our study indicate that circZEB1 had oncogenic function in BC by focusing on circZEB1/miR-337-3p/OGT and YBX1. It might be inferred that circZEB1 could be a promising new target for BC treatment.
摘要：
■越来越多的研究表明，近年来，环状RNA（circularRNAs）对恶性肿瘤的生长变得越来越重要。作为乳腺癌(BC)治疗靶标的理想候选物的CircRNAs仍然不存在。
■在我们的研究中，探索了BC进展中失调的circRNAs，我们使用公开可用的数据集(GSE101124和GSE101122)分析了BC的circRNA表达谱.通过qPCR研究了circZEB1在BC和细胞系中的表达。RNase和放线菌素D用于检查circZEB1的特征。随后通过利用集落形成研究了circZEB1的功能，管形成,transwell分析，和异种移植动物模型。RNA免疫沉淀(RIP),荧光素酶报告基因测定,与LC-MS结合的免疫沉淀（co-IP）测试，和ChIP-seq测定法研究circZEB1在BC中生物活性的分子机制。
■在circRNAs中，我们对hsa_circ_0000228特别感兴趣，它是从癌基因ZEB1剪接的。在BC细胞系中，CircZEB1表达上调。CircZEB1敲低阻止BC细胞迁移和入侵，以及HUVEC从形成管和发展。通过海绵miR-337-3p，功能测试表明circZEB1促进了O-GlcNAcylation，增加YBX1和OGT表达。此外，circZEB1过表达是可逆的，与YBX1敲除相反，这主要导致多种癌基因的下调。
■我们的研究表明，通过关注circZEB1/miR-337-3p/OGT和YBX1，circZEB1在BC中具有致癌功能。可以推断circZEB1可能是BC治疗的有希望的新靶标。
■在我们的研究中，探索了BC进展中失调的circRNAs，我们使用公开可用的数据集(GSE101124和GSE101122)分析了BC的circRNA表达谱.通过qPCR研究了circZEB1在BC和细胞系中的表达。RNase和放线菌素D用于检查circZEB1的特征。随后通过利用集落形成研究了circZEB1的功能，管形成,transwell分析，和异种移植动物模型。RNA免疫沉淀(RIP),荧光素酶报告基因测定,与LC-MS结合的免疫沉淀（co-IP）测试，和ChIP-seq测定法研究circZEB1在BC中生物活性的分子机制。
■在circRNAs中，我们对hsa_circ_0000228特别感兴趣，它是从癌基因ZEB1剪接的。在BC细胞系中，CircZEB1表达上调。CircZEB1敲低阻止BC细胞迁移和入侵，以及HUVEC从形成管和发展。通过海绵miR-337-3p，功能测试表明circZEB1促进了O-GlcNAcylation，增加YBX1和OGT表达。此外，circZEB1过表达是可逆的，与YBX1敲除相反，这主要导致多种癌基因的下调。
■我们的研究表明，通过关注circZEB1/miR-337-3p/OGT和YBX1，circZEB1在BC中具有致癌功能。可以推断circZEB1可能是BC治疗的有希望的新靶标。
