Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 422, Houston, TX, 77030, USA.
Department of Medical Biology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.
Mol Cell Biochem. 2021 May;476(5):2075-2084. doi: 10.1007/s11010-021-04063-y. Epub 2021 Jan 30.
Breast cancer is a highly heterogeneous group of human cancer with distinct genetic, biological and clinicopathological features. Triple-negative breast cancer (TNBC) is the most aggressive and metastatic type of breast cancer and associated with poor patient survival. However, the role of UV Radiation Resistance-Associated Gene (UVRAG) in TNBC remains unknown. Here, we report that UVRAG is highly upregulated in all TNBC cells and its knockdown leads to the inhibition of cell proliferation, colony formation and progression of cell cycle, which is associated with and reduced expression of cell cycle related protein expression, including Cyclin A2, B1, D1, cdc2 and cdk6 in TNBC cells. Inhibition of UVRAG also suppressed cell motility, migration and invasion of TNBC cells by inhibition of Integrin β1 and β3 and Src activity. Our findings suggest for the first time that UVRAG expression contributes to proliferation, cell cycle progression, motility/migration and invasion of TNBC cells. Thus, targeting UVRAG could be a potential strategy in breast cancer especially against TNBC.
乳腺癌是一组具有不同遗传、生物学和临床病理特征的高度异质性人类癌症。三阴性乳腺癌（TNBC）是最具侵袭性和转移性的乳腺癌类型，与患者生存不良相关。然而，UV 辐射抗性相关基因（UVRAG）在 TNBC 中的作用尚不清楚。在这里，我们报告 UVRAG 在所有 TNBC 细胞中高度上调，其敲低导致细胞增殖、集落形成和细胞周期进展的抑制，这与细胞周期相关蛋白表达的减少有关，包括 TNBC 细胞中的细胞周期蛋白 A2、B1、D1、cdc2 和 cdk6。UVRAG 的抑制也通过抑制整合素β1 和β3 以及 Src 活性抑制了 TNBC 细胞的运动性、迁移和侵袭。我们的研究结果首次表明，UVRAG 的表达有助于 TNBC 细胞的增殖、细胞周期进程、运动/迁移和侵袭。因此，靶向 UVRAG 可能是一种治疗乳腺癌的潜在策略，尤其是针对 TNBC。
