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LncRNA BDNF-AS suppresses colorectal cancer cell proliferation and migration by epigenetically repressing GSK-3β

Hui Zhi1, Jiayu Lian1

  • 1Department of Anorectal Surgery, ZhouKou Central Hospital, Zhoukou, Henan, China.

Cell Biochemistry and Function
|May 8, 2019
PubMed

Insights

Long non-coding RNA (lncRNA) BDNF-AS acts as a tumor suppressor in colorectal cancer (CRC). It inhibits cancer cell growth and metastasis by downregulating GSK-3β expression through EZH2 recruitment, offering new therapeutic targets for CRC.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Long non-coding RNA (lncRNA) brain-derived neurotrophic factor antisense (BDNF-AS) is implicated in various cancers, but its role in colorectal cancer (CRC) remains unclear.
  • Previous studies suggest lncRNA BDNF-AS acts as a tumor suppressor in other malignancies, yet its specific functions and mechanisms in CRC pathogenesis require elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms and biological roles of lncRNA BDNF-AS in colorectal cancer (CRC).
  • To determine the correlation between lncRNA BDNF-AS expression and CRC progression.
  • To explore the potential of lncRNA BDNF-AS as a therapeutic target for CRC.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and Western blotting to assess lncRNA BDNF-AS and GSK-3β expression in CRC tissues and cell lines.
  • Cell proliferation, migration, and invasion assays to evaluate the functional impact of lncRNA BDNF-AS on CRC cell behavior.
  • RNA pull-down, RNA immunoprecipitation (RIP), and Chromatin immunoprecipitation (ChIP) assays to confirm molecular interactions and epigenetic modifications.

Main Results:

  • LncRNA BDNF-AS expression was significantly decreased in CRC tissues and cell lines, inversely correlating with aggressive tumor behavior.
  • Overexpression of lncRNA BDNF-AS suppressed CRC cell proliferation, migration, and invasion.
  • LncRNA BDNF-AS inhibited glycogen synthase kinase-3β (GSK-3β) expression by recruiting enhancer of Zeste Homologue 2 (EZH2) to the GSK-3β promoter, leading to H3K27me3 enrichment and gene silencing.

Conclusions:

  • LncRNA BDNF-AS functions as a tumor suppressor in colorectal cancer progression.
  • The mechanism involves EZH2-mediated silencing of GSK-3β, highlighting a novel epigenetic regulatory pathway in CRC.
  • LncRNA BDNF-AS represents a potential diagnostic biomarker and therapeutic target for colorectal cancer.
Keywords:
BDNF-ASEZH2GSK-3βcolorectal cancerlong noncoding RNA

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