Excel · study · 2026
Effect of YTHDC2 knockdown on gene expressions in CAL-27 cell line
Listed in NCBI GEO
Oral squamous cell carcinoma (OSCC), a highly prevalent and poor-prognosis malignancy, is closely associated with tumor metabolic reprogramming, particularly the glutamine-dependent metabolic phenotype.
Description
This study systematically investigates the role of N6-methyladenosine (m6A) modification in OSCC through integrated bioinformatics analysis and functional experiments, focusing on the tumor-suppressive function of the m6A reader YTHDC2 and its regulation of glutamine metabolism.
Analysis based on The Cancer Genome Atlas (TCGA) datasets revealed that YTHDC2 expression was significantly inversely correlated with OSCC malignancy and patient survival. Functional validation showed that YTHDC2 depletion promoted OSCC cell proliferation and stem-like properties, whereas YTHDC2 overexpression markedly suppressed these malignant phenotypes. Mechanistic studies demonstrated that YTHDC2 stabilized VHL mRNA by recognizing m6A modification sites, enhancing VHL protein expression.
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This promoted VHL-mediated ubiquitin-dependent degradation of HIF-1α, leading to transcriptional repression of its downstream target GLS1. Consequently, this blocked glutaminolysis, tricarboxylic acid (TCA) cycle-driven energy production, and glutathione (GSH)-mediated antioxidant pathways. Additionally, low YTHDC2 expression in OSCC tissues was closely associated with DNA hypermethylation at CpG islands (e.g., cg21815882) in its promoter, an epigenetic silencing mechanism that sustains the glutamine-addicted phenotype.
This study first uncovers the core role of the YTHDC2/m6A/VHL/HIF-1α/GLS1 signaling axis in metabolic regulation of OSCC, providing new insights into the molecular basis of glutamine addiction. YTHDC2 not only serves as a prognostic biomarker for OSCC but also highlights its-mediated metabolic pathway as a theoretical basis for developing targeted therapies against glutaminolysis.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301122 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301122 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1284083 ncbi.nlm.nih.gov/bioproject/PRJNA1284083 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Biochemistry and cell biology 69% · Cancer 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE301122 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].anzsrc:group:3101 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (69%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |