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circKDM4C suppresses tumor progression and attenuates doxorubicin resistance by regulating miR-548p/PBLD axis in breast cancer

Oncogene volume 38, pages 6850–6866 (2019)Cite this article

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A Correction to this article was published on 25 March 2021

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Abstract

Increasing evidence has indicated that circular RNAs (circRNAs) play a critical role in cancer development. However, only a small number of circRNAs have been experimentally validated and functionally annotated. In this study, using a high-throughput microarray assay, we identified a novel circRNA, circKDM4C, which was downregulated in breast cancer tissues with metastasis. Furthermore, we analyzed a cohort of breast cancer patients and found that circKDM4C expression was decreased in breast cancer tissues, and lower circKDM4C expression was associated with poor prognosis and metastasis in breast cancer. Functionally, we demonstrated that circKDM4C significantly repressed breast cancer proliferation, metastasis, and doxorubicin resistance in vitro and in vivo. Mechanistically, using a dual-luciferase activity assay and AGO2 RNA immunoprecipitation, circKDM4C was identified as a miR-548p sponge. We also found that PBLD was a direct target of miR-548p, which functioned as a tumor suppressor in breast cancer. Moreover, miR-548p overexpression was able to reverse the circKDM4C-induced attenuation of malignant phenotypes and elevated expression of PBLD in breast cancer cells. Taken together, our data indicate that circKDM4C might have considerable potential as a prognostic biomarker in breast cancer, and support the notion that therapeutic targeting of circKDM4C/miR-548p/PBLD axis may be a promising treatment approach for breast cancer patients.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81272903; No. 81672613; No. 81502285; No. 81602329), China Postdoctoral Science Foundation to NZ (2018M630787), the Key Research and Development Program of Shandong Province (No. 2015GSF118093, No. 2016GSF201119), the Natural Science Foundation of Shandong Province (ZR2014HQ078), the Shandong Science and Technology Development Plan (2016CYJS01A02), and the Special Support Plan for National High Level Talents (“Ten Thousand Talents Program”) to QY.

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Authors and Affiliations

  1. Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China

    Yiran Liang, Xiaojin Song, Yaming Li, Dianwen Han, Tingting Ma, Yuting Sang, Ning Zhang, Xiaoyan Li, Hanwen Zhang, Ying Liu, Yi Duan & Qifeng Yang

  2. Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China

    Peng Su

  3. Department of Urology, Shandong cancer hospital affiliated to Shandong University, Jinan, Shandong, 250117, PR China

    Renbo Guo

  4. Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China

    Bing Chen, Wenjing Zhao, Lijuan Wang & Qifeng Yang

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Liang, Y., Song, X., Li, Y. et al. circKDM4C suppresses tumor progression and attenuates doxorubicin resistance by regulating miR-548p/PBLD axis in breast cancer. Oncogene 38, 6850–6866 (2019). https://doi.org/10.1038/s41388-019-0926-z

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