Omics · study · 2026
SMARCA2 Deficiency Drives BTK Inhibitor Resistance in Mantle Cell Lymphoma by Metabolic Reprogramming via Epigenetic TENT5C Silencing
Listed in NCBI GEO
Mantle cell lymphoma (MCL) remains incurable, and resistance to Bruton's tyrosine kinase inhibitors (BTKis) limits long-term outcomes.
Description
Here, we identified SMARCA2 deletion or low expression as a driver of BTKi resistance and poor survival in MCL. SMARCA2 loss promoted proliferation and resistance by activating oxidative phosphorylation (OXPHOS) and suppressing reactive oxygen species.
Integrative transcriptomic and epigenomic analyses identified TENT5C as a direct SMARCA2 target. SMARCA2 deficiency increased H3K27me3 at the TENT5C locus, reducing chromatin accessibility and silencing its expression. Restoring TENT5C reversed OXPHOS activation and ibrutinib resistance.
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Mechanistically, TENT5C interacted with ATP5A1, and upregulated its inhibitor IF1 to suppress ATP synthase activity. The flavonoid Isoginkgetin synergized with ibrutinib by inhibiting both OXPHOS and BCR signaling in preclinical models. Our findings reveal a SMARCA2-TENT5C-ATP axis linking chromatin remodeling to mitochondrial metabolism, offering novel biomarkers and therapeutic strategies for relapsed/refractory MCL.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326345 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326345 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1357902 ncbi.nlm.nih.gov/bioproject/PRJNA1357902 ↗
project · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE326345 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-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 |