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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.
Abstract:
Long noncoding RNA (lncRNA) FOXC2-AS1 has been reported to act as an oncogene in multiple human cancers. However, the clinical significance, functional role and underlying mechanism of FOXC2-AS1 in gastric cancer (GC) remains largely unknown. Here, we found that FOXC2-AS1 expression was significantly elevated in GC tissues and cells, and overexpression of FOXC2-AS1 indicated advanced TNM stage and shorter overall survival in GC patients. Functionally, knockdown of FOXC2-AS1 attenuated the proliferation, migration and invasion of GC cells, whereas overexpression of FOXC2-AS1 showed the opposite effects. Further investigation revealed that FOXC2-AS1 interacted with FOXC2 mRNA and repressed its degradation. FOXC2-AS1 recruited RNA methyltransferase NSUN2 to FOXC2 mRNA, increasing its m5C level and association with YBX1. Taken together, our findings suggested that FOXC2-AS1 acted as an oncogenic lncRNA by stabilizing FOXC2 mRNA in an m5C-dependent manner, which may provide a novel therapeutic target for GC.
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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