Department of Thyroid and Breast Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Nanjing Medical University, Nanjing, 211166, China.
J Exp Clin Cancer Res. 2021 Jan 12;40(1):29. doi: 10.1186/s13046-021-01830-z.
Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC.
The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1.
Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression.
Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.
环状 RNA（circRNA）是一类新的内源性 RNA，已被证明参与乳腺癌（BC）的发生发展。Hsa_circ_0005273 是由 PTK2 的几个外显子产生的 circRNA。然而，hsa_circ_0005273 在 BC 中的潜在功能作用仍知之甚少。本研究旨在评估 hsa_circ_0005273 在 BC 中的作用。
通过 RT-qPCR 检测 BC 组织和细胞系中 hsa_circ_0005273 和 miR-200a-3p 的表达水平。通过检测 BC 细胞系中 hsa_circ_0005273 敲低后的细胞增殖、迁移和细胞周期来评估其作用。此外，在裸鼠中进行异种移植实验以评估 hsa_circ_0005273 在 BC 中的作用。进行 RNA 免疫沉淀实验、RNA 探针下拉实验、荧光素酶报告基因实验和荧光原位杂交实验以证实 hsa_circ_0005273、miR-200a-3p 和 YAP1 之间的关系。
hsa_circ_0005273 在 BC 组织和细胞系中过表达，而 miR-200a-3p 的表达受到抑制。hsa_circ_0005273 耗竭抑制了 BC 细胞在体外和体内的进展，而过表达 hsa_circ_0005273 则表现出相反的效果。重要的是，hsa_circ_0005273 通过海绵吸附 miR-200a-3p 上调 YAP1 表达并激活 Hippo 通路，从而促进 BC 的进展。
hsa_circ_0005273 通过调节 miR-200a-3p/YAP1 轴并激活 Hippo 信号通路促进 BC 的进展，这可能成为一种有潜力的生物标志物和治疗靶点。
