Geng Zhongli, Wang Wei, Chen Hui, Mao Jianya, Li Zhenguo, Zhou Jing
1Department of Surgery, Affiliated Hospital of Traditional Chinese, Medicine Xinjiang Medical University, 116 Huanghe Road, Urumchi, 830000 Xinjiang China.
Department of Head and Neck Surgery, Qitai County People's Hospital, Changji, Xinjiang China.
Cell Biosci. 2019 Dec 30;9:104. doi: 10.1186/s13578-019-0359-y. eCollection 2019.
Breast cancer is a most common type of cancer in women. Circular RNAs (circRNAs) are involved in cancer development and progression, but their roles and regulatory mechanisms are unclear in breast cancer. Our previous study indicated that has_circ_0001667 (circ_0001667) was up-regulated in breast cancer from the array and might play an oncogenic role, however, the roles of circ_0001667 were not known. This study was aimed to investigate the role and the underlying molecular mechanism of circ_0001667 in breast cancer.
The real-time PCR result showed that circ_0001667 was overexpressed in breast cancer tissues or cell lines compared to the adjacent normal tissues or normal cells. There was a negative relationship between circ_0001667 levels and the life time of breast cancer patients. Meanwhile, the inhibition of circ_0001667 suppressed the proliferation and metastasis of human breast cancer cells. Further bioinformatical analysis indicated that circ_0001667 sponged miR-125a-5p to regulate TAZ expression by Targetscan and miRanda. Dual luciferase reporter assay and western blotting experiments revealed that circ_0001667 negatively regulated miR-125a-5p expression leading to promoting TAZ expression through Hippo signal pathway in breast cancer cells.
This study uncovered that circ_0001667 was a potential breast cancer prognostic marker, as well as a potential therapeutic target to inhibit breast cancer metastasis by circ_0001667/miR-125a-5p/TAZ axis.
乳腺癌是女性中最常见的癌症类型。环状RNA(circRNA)参与癌症的发生和发展,但其在乳腺癌中的作用和调控机制尚不清楚。我们之前的研究表明,在阵列分析中has_circ_0001667(circ_0001667)在乳腺癌中上调,可能发挥致癌作用,然而,circ_0001667的作用尚不清楚。本研究旨在探讨circ_0001667在乳腺癌中的作用及其潜在的分子机制。
实时PCR结果显示,与相邻正常组织或正常细胞相比,circ_0001667在乳腺癌组织或细胞系中过表达。circ_0001667水平与乳腺癌患者的生存期呈负相关。同时,抑制circ_0001667可抑制人乳腺癌细胞的增殖和转移。进一步的生物信息学分析表明,circ_0001667通过Targetscan和miRanda吸附miR-125a-5p来调节TAZ表达。双荧光素酶报告基因检测和蛋白质印迹实验表明,circ_0:01667在乳腺癌细胞中通过Hippo信号通路负向调节miR-125a-5p表达,从而促进TAZ表达。
本研究发现circ_0001667是一种潜在的乳腺癌预后标志物,也是通过circ_0001667/miR-125a-5p/TAZ轴抑制乳腺癌转移的潜在治疗靶点。