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

• Yingjia Li ^[1] ; Xiang Li ^[2]
  1. [1] Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, China
  2. [2] Department of Gynecology, The Third Xiangya Hospital of Central South University, Changsha, China
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 24, Nº. 9, 2022, págs. 1764-1775
• Idioma: inglés
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• Resumen

  • 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.