Although both circular RNAs (circRNAs) and autophagy are associated with the function of breast cancer (BC), whether circRNAs regulate BC progression via autophagy remains unknown. In this study, we aim to explore the regulatory mechanisms and the clinical significance of autophagy-associated circRNAs in BC. Autophagy associated circRNAs were screened by circRNAs deep sequencing and validated by qRT-PCR in BC tissues with high- and low- autophagic level. The biological function of autophagy associated circRNAs were assessed by plate colony formation, cell viability, transwells, flow cytometry and orthotopic animal models. For mechanistic study, RNA immunoprecipitation, circRNAs pull-down, Dual luciferase report assay, Western Blot, Immunofluorescence and Immunohistochemical staining were performed. An autophagy associated circRNA circCDYL was elevated by 3.2 folds in BC tissues as compared with the adjacent non-cancerous tissues, and circCDYL promoted autophagic level in BC cells via the miR-1275-ATG7/ULK1 axis; Moreover, circCDYL enhanced the malignant progression of BC cells in vitro and in vivo. Clinically, increased circCDYL in the tumor tissues and serum of BC patients was associated with higher tumor burden, shorter survival and poorer clinical response to therapy. circCDYL promotes BC progression via the miR-1275-ATG7/ULK1-autophagic axis and circCDYL could act as a potential prognostic and predictive molecule for breast cancer patients.

中文翻译：

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自噬相关的 circRNA circCDYL 增加自噬并促进乳腺癌进展


尽管环状 RNA (circRNA) 和自噬都与乳腺癌 (BC) 的功能相关，但 circRNA 是否通过自噬调节 BC 进展仍不清楚。在本研究中，我们旨在探讨自噬相关的circRNA在BC中的调控机制和临床意义。通过 circRNA 深度测序筛选自噬相关的 circRNA，并通过高自噬水平和低自噬水平的 BC 组织中的 qRT-PCR 进行验证。通过平板集落形成、细胞活力、transwell、流式细胞术和原位动物模型评估自噬相关 circRNA 的生物学功能。对于机制研究，进行了 RNA 免疫沉淀、circRNAs pull-down、双荧光素酶报告测定、Western Blot、免疫荧光和免疫组织化学染色。与邻近非癌组织相比，自噬相关的circRNA circCDYL在BC组织中升高了3.2倍，并且circCDYL通过miR-1275-ATG7/ULK1轴促进BC细胞中的自噬水平；此外，circCDYL在体外和体内增强了BC细胞的恶性进展。临床上，BC患者肿瘤组织和血清中circCDYL的增加与较高的肿瘤负荷、较短的生存期和较差的临床治疗反应相关。 circCDYL 通过 miR-1275-ATG7/ULK1-自噬轴促进 BC 进展，circCDYL 可以作为乳腺癌患者的潜在预后和预测分子。