Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis.
Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis.
复制标题
DOI：
10.3892/ijo.2018.4265
复制
发表时间：
2018-03
影响因子：
5.2
通讯作者：
Ma D
中科院分区：
文献类型：
--
作者：
Wang H;Xiao Y;Wu L;Ma D
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未得到很好的理解。因此，本研究旨在研究circRNA在乳腺癌发生中的表达谱和潜在的调节作用。进行人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著下调的circRNA。机制研究表明，circRNA-000911的表达增强抑制了乳腺癌细胞的增殖、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-449 a鉴定为circRNA-000911相关的microRNA。功能获得和丧失测定表明，miR-449 a拮抗circRNA-000911来调节乳腺癌进展。随后，Notch 1被鉴定为miR-449 a的功能靶标，并且乳腺癌中circRNA-000911的过表达升高了Notch 1的表达。此外，细胞信号转导报告基因阵列和蛋白质印迹分析鉴定了核因子-κB（NF-κB）信号转导作为circRNA-000911/miR-449 a途径的功能靶标。总的来说，我们的研究结果表明circRNA-000911在乳腺癌中发挥着抗癌作用，因此可能成为乳腺癌患者有希望的治疗靶点。因此，circRNA-000911的过表达可能提供一个未来的方向，这可能有助于开发一种新的乳腺癌治疗策略。
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.
登录
查看更多内容
生命过程中环状RNA的新兴景观
影响因子：
4.1
作者：
Qu S;Zhong Y;Shang R;Zhang X;Song W;Kjems J;Li H
通讯作者：
Li H
影响因子：
4
作者：
Heneghan, Helen M.;Miller, Nicola;Kerin, Michael J.
通讯作者：
Kerin, Michael J.
影响因子：
--
作者：
Li H;Li X;Ge X;Jia L;Zhang Z;Fang R;Yang J;Liu J;Peng S;Zhou M;Xiang J;Zeng Z;Zhou W;Xiong W;Xiao G;Fang L;Li GY;Li Z
通讯作者：
Li Z
MiR-449a 通过靶向 CRIP2 促进乳腺癌进展。
影响因子：
--
作者：
Shi W;Bruce J;Lee M;Yue S;Rowe M;Pintilie M;Kogo R;Bissey PA;Fyles A;Yip KW;Liu FF
通讯作者：
Liu FF
影响因子：
13.5
作者：
Han, Dan;Li, Jiangxue;Cao, Xuetao
通讯作者：
Cao, Xuetao