FOXC2-AS1 stabilizes FOXC2 mRNA via association with NSUN2 in gastric cancer cells

Jijun Yan1, Juntao Liu1, Zhengbin Huang1

  • 1Department of General Surgery, Hanchuan People's Hospital, Hanchuan, 431600, Hubei Province, China.

Human Cell
|July 29, 2021
PubMed

Insights

Long noncoding RNA FOXC2-AS1 promotes gastric cancer by stabilizing FOXC2 mRNA. This oncogenic lncRNA enhances cell proliferation, migration, and invasion, offering a potential therapeutic target for gastric cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long noncoding RNA (lncRNA) FOXC2-AS1 is implicated as an oncogene in various human cancers.
  • The specific role and mechanism of FOXC2-AS1 in gastric cancer (GC) are not well understood.

Purpose of the Study:

  • To investigate the clinical significance, functional role, and molecular mechanism of FOXC2-AS1 in gastric cancer.
  • To determine if FOXC2-AS1 could serve as a therapeutic target for GC.

Main Methods:

  • Quantitative real-time PCR to assess FOXC2-AS1 expression in GC tissues and cells.
  • Cell proliferation, migration, and invasion assays following FOXC2-AS1 knockdown or overexpression.
  • RNA immunoprecipitation and Western blot assays to elucidate the interaction between FOXC2-AS1, FOXC2 mRNA, NSUN2, and YBX1.

Main Results:

  • FOXC2-AS1 expression is significantly upregulated in GC tissues and cells.
  • High FOXC2-AS1 levels correlate with advanced TNM stage and poorer overall survival in GC patients.
  • FOXC2-AS1 knockdown inhibits GC cell proliferation, migration, and invasion, while overexpression promotes these processes.
  • FOXC2-AS1 stabilizes FOXC2 mRNA by recruiting NSUN2, leading to increased m5C modification and YBX1 association.

Conclusions:

  • FOXC2-AS1 functions as an oncogenic lncRNA in gastric cancer by stabilizing FOXC2 mRNA via an m5C-dependent mechanism.
  • FOXC2-AS1 represents a potential novel therapeutic target for gastric cancer treatment.

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