FOXN3 Regulates Autophagic Activity to Suppress Drug Resistance in Melanoma Cells

Yaqi Wang1,2, Hui Su1, Xiaopeng Wang1

  • 1Department of Dermatology, Xi'an Jiaotong University The Second Affiliated Hospital, Xi'an, Shaanxi, People's Republic of China.

Abstract

Insights

Forkhead box N3 (FOXN3) is downregulated in melanoma and inhibits cell proliferation and motility. FOXN3 targets Fibrous Sheath Interacting Protein 1 (FSIP1), making it a potential therapeutic target for drug-resistant melanoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Forkhead box N3 (FOXN3) is a transcriptional regulator implicated in tumor development.
  • Its specific role in melanoma pathogenesis and drug resistance remains largely uncharacterized.

Purpose of the Study:

  • To elucidate the biological functions of FOXN3 in the context of melanoma drug resistance.
  • To investigate FOXN3's role in melanoma cell proliferation, motility, and response to Vemurafenib.

Main Methods:

  • Gene expression analysis using GEPIA and Linkedomics databases.
  • In vitro assays including colony formation, scratch wound healing, and Transwell invasion.
  • In vivo xenograft studies in nude mice.
  • Chromatin immunoprecipitation and immunofluorescence to assess protein function and localization.

Main Results:

  • FOXN3 expression is downregulated in melanoma.
  • FOXN3 overexpression suppressed melanoma cell proliferation and motility, while knockdown enhanced them.
  • FOXN3 overexpression reduced autophagic activity; drug-resistant cells showed increased autophagy.
  • FOXN3 binds to the promoter of Fibrous Sheath Interacting Protein 1 (FSIP1), regulating its expression.

Conclusions:

  • FOXN3 is a key regulator in the development of Vemurafenib-resistant melanoma.
  • FOXN3's interaction with FSIP1 contributes to its role in drug resistance.
  • FOXN3 presents a promising therapeutic target for treating drug-resistant melanoma.

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