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NEDD4 E3 ubiquitin protein ligase serves an important role in cutaneous melanoma occurrence and development

Fang Cheng1, Yi Cheng2, Xiaoling Zhao1

  • 1Department of Dermatology, Affiliated Xingtai People's Hospital of Hebei Medical University, Xingtai, Hebei 054001, P.R. China.

Experimental and Therapeutic Medicine
|October 15, 2021
PubMed

Insights

NEDD4 E3 ubiquitin protein ligase (NEDD4) is upregulated in cutaneous melanoma (CMM). Knocking down NEDD4 suppressed CMM cell proliferation and migration by regulating the Notch1/PTEN pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cutaneous melanoma (CMM) is a significant skin cancer.
  • The role of NEDD4 E3 ubiquitin protein ligase (NEDD4) in CMM is not fully understood.

Purpose of the Study:

  • To investigate the effects and mechanisms of NEDD4 in CMM occurrence and development.
  • To analyze NEDD4 expression in CMM tissues and cell lines.
  • To determine the impact of NEDD4 knockdown on CMM cell behavior.

Main Methods:

  • Tissue sample analysis for NEDD4 expression.
  • NEDD4 knockdown using small interfering (si)RNA in SK-MEL-2 and Malme-3M cells.
  • Assays for cell proliferation, apoptosis, invasion, and migration (colony formation, flow cytometry, Transwell, wound-healing).
  • RT-quantitative PCR and western blotting to assess gene and protein expression levels of NEDD4, Notch1, and PTEN.

Main Results:

  • NEDD4 mRNA and protein expression were significantly upregulated in CMM.
  • NEDD4 knockdown decreased cell proliferation and migration, and increased apoptosis.
  • NEDD4 knockdown led to downregulation of NEDD4 and Notch1, and upregulation of PTEN.
  • These changes were observed in SK-MEL-2 and Malme-3M cell lines.

Conclusions:

  • NEDD4 plays a crucial role in CMM development.
  • NEDD4 knockdown effectively suppresses CMM biological activity.
  • The suppressive effects are mediated through the regulation of the Notch1/PTEN pathway in vitro.
Keywords:
NEDD4 E3 ubiquitin protein ligasePTENSK-MEL-2cutaneous melanomamalme-3Mnotch receptor 1

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