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首页> 外文期刊>International journal of oncology >Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis
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Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis

机译：全面的环形RNA分析揭示了circRNA-000911 / miR-449a途径在乳腺癌致癌中的调控作用

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Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers; however their roles in breast tumorigenesis are not yet well understood. Thus, the present study aimed to investigate the expression profiles and potential modulatory effects of circRNAs on breast carcinogenesis. A human circRNA microarray analysis was performed to screen for abnormally expressed circRNAs in breast cancer tissue and circRNA-000911 was identified as a circRNA which was significantly downregulated in breast cancer cells. Mechanistic investigations suggested that the enhanced expression of circRNA-000911 suppressed cell proliferation, migration and invasion, and promoted the apoptosis of breast cancer cells. By using a biotin-labeled circRNA-000911 probe to perform RNA precipitation in breast cancer cells, we identified miR-449a as the circRNA-000911-associated microRNA. Gain- and loss-of-function assays indicated that miR-449a antagonized circRNA-000911 to regulate breast cancer progression. Subsequently, Notch1 was identified as the functional target of miR-449a, and the overexpression of circRNA-000911 in breast cancer elevated Notch1 expression. Furthermore, Cignal Signal Transduction Reporter Array and western blot analysis identified nuclear factor-κB (NF-κB) signaling as a functional target of the circRNA-000911/miR-449a pathway. On the whole, our findings indicate that circRNA-000911 plays an anti-oncogenic role in breast cancer and may thus serve as a promising therapeutic target for patients with breast cancer. Therefore, the overexpression of circRNA-000911 may provide a future direction which may aid in the development of a novel treatment strategy for breast cancer.
机译：环状RNA（circRNA）是人类癌症发生和发展的关键调控因子。然而，它们在乳腺肿瘤发生中的作用尚不十分清楚。因此，本研究旨在研究circRNA对乳腺癌致癌作用的表达谱和潜在的调节作用。进行了人circRNA微阵列分析以筛选乳腺癌组织中异常表达的circRNA，并且circRNA-000911被鉴定为在乳腺癌细胞中显着下调的circRNA。机理研究表明，circRNA-000911的增强表达抑制了细胞的增殖，迁移和侵袭，并促进了乳腺癌细胞的凋亡。通过使用生物素标记的circRNA-000911探针在乳腺癌细胞中进行RNA沉淀，我们将miR-449a鉴定为与circRNA-000911相关的microRNA。功能获得和功能丧失分析表明，miR-449a拮抗circRNA-000911以调节乳腺癌的进展。随后，Notch1被鉴定为miR-449a的功能靶标，而circRNA-000911在乳腺癌中的过表达提高了Notch1的表达。此外，Cignal Signal Transduction Reporter Array和Western blot分析确定了核因子-κB（NF-κB）信号传导是circRNA-000911 / miR-449a途径的功能靶标。总体而言，我们的发现表明，circRNA-000911在乳腺癌中具有抗癌作用，因此可能成为乳腺癌患者的有希望的治疗靶标。因此，circRNA-000911的过表达可能会提供一个未来的方向，可能有助于开发一种新的乳腺癌治疗策略。

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