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LncRNA UCA1 attenuated the killing effect of cytotoxic CD8 + T cells on anaplastic thyroid carcinoma via miR-148a/PD-L1 pathway

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Abstract

Background

LncRNAs play an important role in the regulation of the killing effect of cytotoxic CD8 + T cells in various cancers. However, the role and underlying mechanisms of UCA1 in the killing effect of cytotoxic CD8 + T cells in anaplastic thyroid carcinoma (ATC) are not clear.

Methods

UCA1, miR-148a, and PD-L1 expression were detected by quantitative real-time PCR and/or Western blot. The ratio of PD-L1+ATC cells/ATC cells was determined using flow cytometry. The ability of CD8 + T cells to kill target ATC cells was detected by Chromium-51 (51Cr) release assay. The targeted relationship between UCA1 and miR-148a was confirmed by dual-luciferase reporter gene assay.

Results

UCA1 and PD-L1 expression levels were elevated in ATC tissues and cells. Silencing UCA1 and PD-L1 enhanced the killing effect of cytotoxic CD8 + T cells on ATC cells. UCA1 negatively regulated the expression of miR-148a, and miR-148a targeted PD-L1 to down-regulate its expression. Besides, we found that UCA1 attenuated the killing effect of cytotoxic CD8 + T cells and reduced cytokine secretion through PD-L1 and miR-148a. Finally, silencing UCA1 or PD-L1 in ATC cells restored the suppression of the killing effect of CD8 + T cells in vivo.

Conclusion

UCA1 attenuated the killing effect of cytotoxic CD8 + T cells on ATC cells through the miR-148a/PD-L1 pathway.

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Authors and Affiliations

  1. Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Rd., Zhengzhou, 450052, People’s Republic of China

    Xiaoming Wang, Jian Zheng, Cuixian Yao & Xiubo Lu

  2. Key Laboratory of Thyroid Tumor, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China

    Xiaoming Wang, Jian Zheng, Cuixian Yao & Xiubo Lu

  3. Operation Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China

    Yan Zhang

Authors
  1. Xiaoming Wang
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  2. Yan Zhang
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  3. Jian Zheng
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  4. Cuixian Yao
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  5. Xiubo Lu
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Contributions

XW designed this experiment and performed the experiments. XW and YZ edited this manuscript. YZ and JZ collected data and performed the statistical analysis. JZ, CY and MT revised this manuscript. XL made substantial contributions to the conception, design, and critical revision of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xiubo Lu.

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Conflict of interest

The authors have no actual or potential conflicts of interest to declare.

Ethical approval

The study was approved by the ethics committee of The First Affiliated Hospital of Zhengzhou University.

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Supplementary file1 Supplementary Fig. 1 The flow chart of the pathway mechanism (TIF 404 kb)

262_2020_2753_MOESM2_ESM.tif

Supplementary file2 Supplementary Fig. 2 The effect of miR-148a on the expression of UCAI in cells and the verification of the interaction between UCA1 and miR-148a. A. Hth74 and 8505C cells were transfected with miR-148a mimic, UCA1 expression was detected by qRT-PCR. *P < 0.05, **P < 0.01 vs. NC. B. The interaction between UCA1 and miR-148a was detected by RNA pull-down assay. **P < 0.01 vs. Bio-NC-probe. NC: negative control (TIF 130 kb)

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Wang, X., Zhang, Y., Zheng, J. et al. LncRNA UCA1 attenuated the killing effect of cytotoxic CD8 + T cells on anaplastic thyroid carcinoma via miR-148a/PD-L1 pathway. Cancer Immunol Immunother 70, 2235–2245 (2021). https://doi.org/10.1007/s00262-020-02753-y

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  • DOI: https://doi.org/10.1007/s00262-020-02753-y

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