Velayuthaprabhu Shanmugam (2025) Targeting the lncRNA RBM5-AS1/GCN5 axis under fasting conditions reprograms Glycolysis and induces apoptosis in ovarian cancer cells. Targeting the lncRNA RBM5-AS1/GCN5 axis under fasting conditions reprograms Glycolysis and induces apoptosis in ovarian cancer cells, 52 (691). pp. 1-22.
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Targeting the lncRNA RBM5-AS1-GCN5 axis under fasting conditions reprograms Glycolysis and induces apoptosis in ovarian cancer cells.pdf - Published Version
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Abstract
Background Ovarian cancer is a highly aggressive malignancy influenced by complex molecular interactions, including
those involving long non-coding RNAs. RBM5-AS1, a nuclear-retained lncRNA, interacts with GCN5 to acetylate PGC-1α,
thereby enhancing the Warburg effect. Although fasting is known to exert antitumor effects by modulating lncRNAs and acti
vating PGC-1α, its impact on the RBM5-AS1/GCN5 axis in ovarian cancer remains underexplored. This study evaluates the
therapeutic efficacy of RBM5-AS1 knockdown and GCN5 inhibition under fasting-mimicked conditions in SKOV3 cells.
Methods and results The findings of cytotoxicity assays revealed a dose-dependent decrease in cell viability, with the fast
ing + siRNA + MB-3 combination showing the most potent anticancer effect. LDH assays confirmed enhanced membrane
damage in this group. Migration assays demonstrated reduced motility, while DAPI and acridine orange/ethidium bromide
staining indicated significant apoptotic features present in fasting + siRNA + MB-3-treated ovarian cancer cells. Colony for
mation was markedly inhibited under the combination treatment, confirming suppression of clonogenic potential. Flow
cytometry analysis revealed > 80% late apoptotic/necrotic cells in the fasting + siRNA + MB-3 group. Gene expression analy
sis further showed downregulation of Warburg-related genes (PDK1/2/3/4, LDH, GLUT1/3/4) and upregulation of PDH and
pro-apoptotic markers (Caspase, Bax), alongside reduced PGC-1α acetylation.
Conclusion These findings indicate that fasting enhances the therapeutic effect of RBM5-AS1 knockdown and GCN5 inhi
bition, leading to a significant disruption of glycolytic metabolism and promoting apoptosis. This combinatorial approach
highlights a promising metabolic and epigenetic strategy for ovarian cancer treatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Ovarian cancer · LncRNA RBM5-AS1 · GCN5 · PGC-1α acetylation Warburg effect · Fasting |
| Divisions: | PSG College of Arts and Science > Department of Biochemistry |
| Depositing User: | Dr. B Sivakumar |
| Date Deposited: | 03 Dec 2025 05:49 |
| Last Modified: | 03 Dec 2025 05:49 |
| URI: | https://ir.psgcas.ac.in/id/eprint/2551 |
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