2. Academic Validation
  3. KLF4 suppresses anticancer effects of brusatol via transcriptional upregulating NCK2 expression in melanoma

KLF4 suppresses anticancer effects of brusatol via transcriptional upregulating NCK2 expression in melanoma

  • Biochem Pharmacol. 2024 May:223:116197. doi: 10.1016/j.bcp.2024.116197.
Xiaodong Li 1,  Yuankuan Jiang 2,  Ying Wang 3,  Na Li 4,  Shumeng Zhang 2,  Kejia Lv 2,  Renchuan Jia 2,  Tianfu Wei 2,  Xiaojie Li 5,  Chuanchun Han 6,  Jingrong Lin 7
Affiliations

Affiliations

  • 1 Department 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.
  • 2 Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian 116044, PR China.
  • 3 Institute of Cancer Stem Cell of Dalian Medical University, Dalian 116044, PR China.
  • 4 National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, PR China.
  • 5 College of Stomatology Dalian Medical University, Dalian 116044, PR China. Electronic address: xiaojieli0504@dmu.edu.cn.
  • 6 Institute of Cancer Stem Cell of Dalian Medical University, Dalian 116044, PR China. Electronic address: hanzc@dmu.edu.cn.
  • 7 Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian 116044, PR China. Electronic address: linjingrong1@firsthosp-dmu.com.
PMID: 38583810 DOI: 10.1016/j.bcp.2024.116197
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.

Keywords

KLF4; Melanoma; NCK2.

Figures
Products