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Circ_0008500 Knockdown Improves Radiosensitivity and Inhibits Tumorigenesis in Breast Cancer Through the miR-758-3p/PFN2 Axis

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Breast cancer is one of the most common malignancies worldwide. Circular RNAs (CircRNAs) were revealed to be implicated in the development of breast cancer. In this research, we aimed to investigate the role and underlying mechanism of circ_0008500 in the development and radiosensitivity of breast cancer. Using real-time quantitative PCR (RT-qPCR) and western blot, we found that hsa_circ_0008500 (circ_0008500) and profilin 2 (PFN2) were increased, while microRNA-758-3p (miR-758-3p) was decreased in breast cancer tissues and cells. Cell viability, the number of colonies, proliferation and apoptosis were detected using CCK-8, colony formation, EdU assays and flow cytometry, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were devoted to test the interaction between miR-758-3p and circ_0008500 or PFN2. The results showed that circ_0008500 knockdown inhibited cell growth, and facilitated cell apoptosis and radiosensitivity in breast cancer cells in vitro. Moreover, circ_0008500 regulated PFN2 expression by sponging miR-758-3p. Functionally, circ_0008500 knockdown regulated cell behaviors and radiosensitivity by targeting miR-758-3p to downregulate PFN2 expression in vitro. Additionally, in vivo tumor formation assay and immunohistochemistry (IHC) assay demonstrated that circ_0008500 knockdown enhanced the radiosensitivity and repressed tumor growth in vivo. In conclusion, circ_0008500 inhibition promoted the radiosensitivity and restrained the development of breast cancer by downregulating PFN2 expression via targeting miR-758-3p.

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Funding

This study was supported by Scientific Research Fund Project of Hebei Provincial Health and Family Planning Commission. (No. 20201103).

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Authors and Affiliations

  1. Department of Radiotherapy, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050035, China

    Deyou Kong, Dongxing Shen, Zhikun Liu, Jun Zhang & Jian Zhang

  2. Breast Center, the Fourth Hospital of Hebei Medical University, Yuhua District, No. 169 Tianshan Street, Shijiazhuang, 050035, China

    Cuizhi Geng

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  1. Deyou Kong
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  2. Dongxing Shen
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Correspondence to Cuizhi Geng.

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Kong, D., Shen, D., Liu, Z. et al. Circ_0008500 Knockdown Improves Radiosensitivity and Inhibits Tumorigenesis in Breast Cancer Through the miR-758-3p/PFN2 Axis. J Mammary Gland Biol Neoplasia 27, 37–52 (2022). https://doi.org/10.1007/s10911-022-09514-w

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