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TRG16, targeted by miR-765, inhibits breast cancer stem cell-like properties via regulating the NF-κB pathway

Abstract

Previous studies reported that cancer stem cells (CSCs) might be responsible for drug resistance and cancer progression. Transformation-Related Gene 16 Protein (TRG16), a pseudokinase, was reported to be a suppressor in some types of cancer and its overexpression impaired hepatocellular carcinoma cell stemness. However, the function of TRG16 in BC remains unclear. We found that TRG16 expression was significantly downregulated in BC tissues compared with adjacent tissues (n = 40; P < 0.001) and BC patients with lower expression of TRG16 had a worse prognosis. Forced expression of TRG16 inhibited BC stem cell-like properties as evidenced by decreased CD44-positive cells (CSC marker), reduced mammosphere quantity, and downregulated Nanog, aldehyde dehydrogenase, octamer-binding transcription factor 4, and SRY-box transcription factor 2 expression (CSC markers). Moreover, TRG16 overexpression inhibited self-renewal and invasion capabilities of BC cells in vitro as well as tumor growth in vivo but increased cisplatin sensitivity. However, TRG16 silencing had the opposite effects. Further mechanistic studies revealed that TRG16 was targeted and negatively regulated by miR-765, a facilitator of BC progression. TRG16 could suppress the activation of the NF-κB pathway in BC cells, which is a positive pathway in BC progression and contributes to the maintenance of cancer cell stemness. In conclusion, the results above demonstrate that TRG16, negatively regulated by miR-765, may inhibit the BC progression by regulating BC stem cell-like properties and this inhibition may be mediated by the NF-κB pathway. Our findings indicate that TRG16 may be a potential therapeutic targetable node for BC.

Graphical abstract

TRG16, negatively regulated by miR-765, may inhibit the BC progression through regulating BC stem cell-like properties and this inhibition may be mediated by the NF-κB pathway.

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Data availability

The data will be made available from the corresponding author on reasonable request.

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Funding

This research was funded by the Hospital Project of Shengjing Hospital of China Medical University.

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FC: Conceptualization, writing—original draft. XJ and LC: Data curation, investigation, and methodology. GH: Formal analysis and software. SH: Supervision, writing-reviewing and editing.

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Correspondence to Sijia Han.

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Chi, F., Jin, X., Chen, L. et al. TRG16, targeted by miR-765, inhibits breast cancer stem cell-like properties via regulating the NF-κB pathway. Mol Cell Biochem (2022). https://doi.org/10.1007/s11010-022-04480-7

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  • DOI: https://doi.org/10.1007/s11010-022-04480-7

Keywords

  • Breast cancer
  • TRG16
  • Cancer stem cell-like properties
  • The NF-κB pathway
  • miR-765