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. 2022 Sep;24(9):1764-1775.
doi: 10.1007/s12094-022-02831-w. Epub 2022 Apr 26.

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

Yingjia Li  1 , Xiang Li  2
Affiliations

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

Yingjia Li et al. Clin Transl Oncol. 2022 Sep.

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.

Keywords: Pyroptosis; Radioresistance; Triple-negative breast cancer; miR-1290.

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