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miR-1290 modulates the radioresistance of triple-negative breast cancer by targeting NLRP3-mediated pyroptosis

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Abstract

Purpose

To explore the roles and underlying mechanisms of miR-1290 in determining the sensitivity of triple-negative breast cancer (TNBC) to radiation therapy.

Methods

ELISA was performed to detect the levels of IL-18 and IL-1β in radiosensitive cells and serum samples. The level of miR-1290 in radiosensitive cells and tissues was assessed by qRT–PCR assay. A luciferase reporter assay was performed to confirm NLRP3 as the target of miR-1290. Functionally, the roles of miR-1290 in TNBC radioresistance were analyzed by transfection of either miR-1290 mimic or miR-1290 inhibitor. Moreover, the involvement of the miR-1290/NLRP3 axis in TNBC radioresistance was analyzed by experiments with a miR-1290 mimic and NLRP3 overexpression. MTT and colony formation assays were used to detect radiation-induced cell viability and proliferation. qRT–PCR and western blot assays were used to detect pyroptosis markers (NLRP3, ACS and caspase-1).

Results

The results showed that radioresistance in TNBC cells was associated with a reduction in pyroptosis. miR-1290 expression was increased in radioresistant cells, and it had higher expression levels in the radioresistant tumor tissues of TNBC patients compared to the radiosensitive samples. The miR-1290 mimic suppressed radiation-induced pyroptosis and reduced the radiosensitivity of TNBC cells. Moreover, we found that NLRP3 was a potential target of miR-1290. Overexpression of NLRP3 partly reversed the effects of miR-1290 on pyroptosis and radioresistance. The mouse models showed that miR-1290 suppressed tumor size, tumor weight and pyroptosis.

Conclusions

miR-1290/NLRP3-mediated pyroptosis may play an important role in determining radioresistance in TNBC and serve as a novel therapeutic option.

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Author information

Authors and Affiliations

  1. Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, 410013, China

    Yingjia Li

  2. Department of Gynecology, The Third Xiangya Hospital of Central South University, Tongzipo Road 138, Changsha, 410013, China

    Xiang Li

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  1. Yingjia Li
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  2. Xiang Li
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Contributions

YL conceived the study, designed the study and drafted the manuscript. XL collected, analyzed and interpreted the experimental data. YL and XL revised the manuscript for important intellectual content. Both authors read and approved the final manuscript.

Corresponding author

Correspondence to Xiang Li.

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The authors declare that they have no conflicts of interest.

Ethical approval

The study was approved by the Ethical Committee of the Third Xiangya Hospital of Central South University (ethics approval codes: 22040 and LLSC(LA)2018-053) and conducted in accordance with ethical standards.

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Yes.

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Cite this article

Li, Y., Li, X. miR-1290 modulates the radioresistance of triple-negative breast cancer by targeting NLRP3-mediated pyroptosis. Clin Transl Oncol 24, 1764–1775 (2022). https://doi.org/10.1007/s12094-022-02831-w

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  • DOI: https://doi.org/10.1007/s12094-022-02831-w

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