Autophagy-associated circRNA circCDYL augments autophagy and promotes breast cancer progression
Autophagy-associated circRNA circCDYL augments autophagy and promotes breast cancer progression
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自噬相关的 circRNA circCDYL 增强自噬并促进乳腺癌进展
DOI：
10.1186/s12943-020-01152-2
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发表时间：
2020-03-25
期刊：
影响因子：
37.3
通讯作者：
Gong, Chang
中科院分区：
文献类型：
--
作者：
Liang, Gehao;Ling, Yun;Gong, Chang
尽管环状rna （circRNAs）和自噬都与乳腺癌（BC）的功能相关，但环状rna是否通过自噬调节BC的进展仍不清楚。在本研究中，我们旨在探讨BC中自噬相关circrna的调控机制及其临床意义。方法采用circRNAs深度测序技术筛选自噬相关环状rna，并采用qRT-PCR技术在高自噬水平和低自噬水平的BC组织中进行验证。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环状rna的生物学功能。机制研究采用RNA免疫沉淀、环状RNA下拉、双荧光素酶报告试验、Western Blot、免疫荧光和免疫组织化学染色。结果与癌旁非癌组织相比，与自噬相关的环状rna circCDYL在BC组织中升高了3.2倍，circCDYL通过miR-1275-ATG7/ULK1轴促进BC细胞的自噬水平；此外，circCDYL在体外和体内均能促进BC细胞的恶性进展。在临床上，BC患者肿瘤组织和血清中circCDYL的升高与肿瘤负担加重、生存期缩短和临床治疗反应较差相关。结论circCDYL通过miR-1275-ATG7/ ulk1自噬轴促进BC进展，circCDYL可作为乳腺癌患者潜在的预后和预测分子。
BackgroundAlthough 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.MethodsAutophagy 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.ResultsAn 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.ConclusionscircCDYL 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.