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Circular RNA hsa_circ_0001598 promotes programmed death-ligand-1-mediated immune escape and trastuzumab resistance via sponging miR-1184 in breast cancer cells

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Abstract

Approximately 25% of breast cancer (BC) patients are HER2-positive. Trastuzumab is used as a targeted therapy drug to treat HER2-positive BC patients; however, the drug resistance remains a big challenge. Circular RNAs (circRNAs) are reported to be involved in drug resistance, but the role of circ_0001598 has never been studied in BC. First, we identified the expression of circ_0001598 by RT-qPCR in BC. The gain-of-function and loss-of-function studies were applied to study the functional roles of circ_0001598 and its target gene. We observed upregulation of circ_0001598 in BC tissues, especially in trastuzumab-resistant BC samples. We further identified that miR-1184 is a functional target of circ_0001598. Moreover, it was found that programmed death-ligand 1 (PD-L1) was a direct target of miR-1184. The oncogenic effects of circ_0001598 in promoting BC cell growth, trastuzumab-resistance, PD-L1 expression, and escaping of CD8 T cell killing were abolished after the restoration of miR-1184. In conclusion, we demonstrate that circ_0001598/miR-1184/PD-L1 signaling plays a crucial role in the regulation of BC progression and trastuzumab-resistance phonotypes, which suggests that circ_0001598 may be a molecular target to treat HER2-positive BC patients.

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The data to generate the figures could be obtained upon reasonable request to the authors.

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Authors and Affiliations

  1. Department of Oncology, Zibo Central Hospital, No.54 West Gongqingtuan Road, Zhangdian District, Zibo, 255022, Shandong, China

    Li Huang, Jing Ma & Min Cui

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  1. Li Huang
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  2. Jing Ma
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Correspondence to Min Cui.

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Ethics committee of Zibo Central Hospital has approved this study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Huang, L., Ma, J. & Cui, M. Circular RNA hsa_circ_0001598 promotes programmed death-ligand-1-mediated immune escape and trastuzumab resistance via sponging miR-1184 in breast cancer cells. Immunol Res 69, 558–567 (2021). https://doi.org/10.1007/s12026-021-09237-w

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  • DOI: https://doi.org/10.1007/s12026-021-09237-w

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