Tumor Biology

, Volume 37, Issue 10, pp 13733–13742 | Cite as

Knockdown of miR-182 promotes apoptosis via regulating RIP1 deubiquitination in TNF-α-treated triple-negative breast cancer cells

  • Like Wo
  • Dezhao Lu
  • Xidong GuEmail author
Original Article


Overexpression of microRNA-182 (miR-182) is found in multiple cancers, but the association of miR-182 expression with the sensitivity of triple-negative breast cancer (TNBC) cells to tumor necrosis factor-alpha (TNF-α) remains unknown. In this study, up-regulation of miR-182 was validated in TNBC patients and cell lines. Knockdown of miR-182 was observed to hinder the proliferation of BT-549 cells. More importantly, knockdown of miR-182 significantly promoted the apoptosis induced by TNF-α treatment in BT-549. JC-1 staining and western blot assays revealed that the K63-linked ubiquitin chains on receptor-interacting protein 1 (RIP1) were removed and the outer mitochondrial membrane potential (MMP) and permeability was altered upon combination of TNF-α with anti-miR-182. We then demonstrated that knockdown of miR-182 up-regulated the expression of cylindromatosis (CYLD) deubiquitinase, which promoted the formation of death-inducing signaling complex (DISC) and subsequent caspase-8 activation in TNF-α-treated BT-549 cells. Collectively, the results of the present study improve our understanding of the role of miR-182 in TNBC, knockdown of which facilitates the degradation of ubiquitin chains on RIP1, leading to the caspase-8 activation and apoptosis in TNF-α-treated TNBC cells. This may be valuable for the development of cancer therapy.


TNBC TNF-α miR-182 CYLD Deubiquitination 



This study is supported by the medical and health technology plan of Zhejiang Province (grant no.: 2015KYB268) and the TCM plan of Zhejiang Province (grant no.: 2010ZB038).

Compliance with ethical standards

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Breast SurgeryFirst Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouChina
  2. 2.College of Life ScienceZhejiang Chinese Medical UniversityHangzhouChina

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