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Updated: Jun 29, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
KLF4 suppresses anticancer effects of brusatol via transcriptional upregulating NCK2 expression in melanoma
Xiaodong Li1, Yuankuan Jiang2, Ying Wang3
1Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian 116044, PR China; Institute of Cancer Stem Cell of Dalian Medical University, Dalian 116044, PR China.
Abstract:
Brusatol (Bru), a main extract from traditional Chinese medicine Brucea javanica, has been reported to exist antitumor effect in many tumors including melanoma. However, the underlying mechanism in its anti-melanoma effect still need further exploration. Here, we reported that the protein expression of KLF4 in melanoma cells were significantly downregulated in response to brusatol treatment. Overexpression of KLF4 suppressed brusatol-induced melanoma cell apoptosis; while knockdown of KLF4 enhanced antitumor effects of brusatol on melanoma cells not only in vitro but also in vivo. Further studies on the mechanism revealed that KLF4 bound to the promoter of NCK2 directly and facilitated NCK2 transcription, which suppressed the antitumor effect of brusatol on melanoma. Furthermore, our findings showed that miR-150-3p was dramatically upregulated under brusatol treatment which resulted in the downregulation of KLF4. Our results suggested that the miR-150-3p/KLF4/NCK2 axis might play an important role in the antitumour effects of brusatol in melanoma.
Insights
Brusatol, a traditional Chinese medicine extract, shows antitumor effects against melanoma by downregulating KLF4. This pathway involves miR-150-3p and NCK2, offering new therapeutic strategies for melanoma treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Brusatol, derived from Brucea javanica, exhibits known antitumor properties.
- The precise mechanisms underlying Brusatol's anti-melanoma effects require further elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms of Brusatol's anti-melanoma activity.
- To identify key molecular players involved in Brusatol's therapeutic effects on melanoma cells.
Main Methods:
- Analysis of KLF4 protein expression in melanoma cells treated with Brusatol.
- In vitro and in vivo studies involving KLF4 overexpression and knockdown.
- Investigation of KLF4 binding to the NCK2 promoter and its transcriptional activity.
- Assessment of miR-150-3p expression levels following Brusatol treatment.
Main Results:
- Brusatol treatment significantly downregulated KLF4 protein expression in melanoma cells.
- KLF4 overexpression inhibited Brusatol-induced apoptosis, while KLF4 knockdown enhanced Brusatol's antitumor effects.
- KLF4 directly binds to the NCK2 promoter, promoting its transcription and suppressing Brusatol's efficacy.
- Brusatol treatment led to a significant upregulation of miR-150-3p, which in turn downregulated KLF4.
Conclusions:
- The miR-150-3p/KLF4/NCK2 signaling axis is a critical mediator of Brusatol's antitumor effects in melanoma.
- Targeting this axis could represent a novel therapeutic strategy for melanoma treatment.
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