FOXD2-AS1 Binding to MYC Activates EGLN3 to Affect the Malignant Progression of Clear Cell Renal Cell Carcinoma

Zhigang Huang1, Bin Liu2, Xiaoju Li1

  • 1Urology Department, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China.

Insights

Long noncoding RNA FOXD2-AS1 promotes clear cell renal cell carcinoma (ccRCC) progression by upregulating EGLN3 expression through MYC recruitment. This FOXD2-AS1/MYC/EGLN3 axis accelerates ccRCC cell proliferation, migration, and invasion.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Long noncoding RNAs (lncRNAs) play crucial roles in cancer, but their regulatory mechanisms remain unclear.
  • FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is highly expressed in various cancers, including clear cell renal cell carcinoma (ccRCC).

Purpose of the Study:

  • To investigate the regulatory mechanism of FOXD2-AS1 in ccRCC.
  • To elucidate the influence of FOXD2-AS1 on ccRCC cell functions.
  • To provide insights into ccRCC treatment and prognosis.

Main Methods:

  • Differential expression and survival analyses to identify prognostic lncRNAs.
  • lncRNA-transcription factor-mRNA triplet prediction using lncMAP.
  • RNA immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays to verify molecular interactions.
  • In vitro cell function assays and in vivo mouse experiments for validation.

Main Results:

  • FOXD2-AS1 and Egl-9 family hypoxia-inducible factor 3 (EGLN3) expression are elevated in ccRCC.
  • FOXD2-AS1 promotes ccRCC cell proliferation, migration, and invasion by upregulating EGLN3.
  • FOXD2-AS1 recruits MYC to the EGLN3 promoter region, mediating its regulatory effect.
  • The FOXD2-AS1/MYC/EGLN3 axis accelerates ccRCC progression in vitro and in vivo.

Conclusions:

  • FOXD2-AS1 acts as a key oncogenic lncRNA in ccRCC.
  • The FOXD2-AS1/MYC/EGLN3 signaling pathway is a potential therapeutic target for ccRCC.
  • Understanding this axis offers a theoretical basis for refining ccRCC prognoses.

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