Suppression of CircPVT1 Potentiates 5-Fluorouracil-Driven Programmed Cell Death in SK-MEL-37 Malignant Melanoma Cells: Role of the miR-203a-3p/FGF2 Regulatory Cascade
Archives of Advances in Biosciences,
Vol. 17 No. 1 (2026),
28 April 2026
https://doi.org/10.22037/aab.v17i1.52479
Abstract
Background: The circular RNA, known as CircPVT1, functions as an oncogenic molecule across several malignancies, including cutaneous melanoma. Nevertheless, how it influences chemotherapeutic responsiveness in melanoma remains poorly defined. This work sought to determine whether targeted suppression of CircPVT1 via small interfering RNA could improve the cytotoxic activity of 5-fluorouracil (5-FU) against SK-MEL-37 melanoma cells and to evaluate whether the miR-203a-3p/FGF2 pathway participates in this process.
Methods: SK-MEL-37 cultures were assigned to five experimental conditions: untreated controls, non-targeting scrambled siRNA (40 nM), CircPVT1-directed siRNA (40 nM), 5-FU alone (500 µM), and the siRNA/5-FU combination. Transfection employed TurboFect reagent. Following a 48-hour exposure, viability was evaluated through MTT colorimetry. Apoptotic rates were determined via Annexin V-FITC/propidium iodide dual labeling coupled with flow cytometry. Quantitative real-time PCR measured transcript levels of CircPVT1, miR-203a-3p, FGF2, Bax, Bcl-2, and Caspase-3. Bioinformatic tools (circInteractome, TargetScan, miRDB) predicted possible interactions within the CircPVT1/miR-203a-3p/FGF2 network.
Results: In silico analysis revealed a potential miR-203a-3p docking site inside CircPVT1 and identified FGF2 as a genuine miR-203a-3p target carrying a conserved 3′UTR recognition sequence. MTT data showed that anti-CircPVT1 siRNA lowered viability to 48.3% of control values, whereas 5-FU alone dropped viability to 44.2%. The combined regimen produced the strongest reduction, yielding 28.6% viability (p<0.001 versus controls; p<0.01 versus each monotherapy). Flow cytometry indicated that the combination elevated late-stage apoptosis to 24.3%, compared with 17.9% for siRNA alone and 15.7% for 5-FU alone (p<0.001). qRT-PCR revealed that the combination upregulated miR-203a-3p by 5.76-fold and Bax by 2.36-fold, while downregulating CircPVT1 to 0.22-fold, FGF2 to 0.11-fold, and Bcl-2 to 0.18-fold. The Bax/Bcl-2 ratio rose from 1.0 (controls) to 13.1 in the combination arm
Conclusion: Our findings indicate that CircPVT1 knockdown markedly boosts 5-FU-provoked apoptosis in SK-MEL-37 melanoma cells, an effect likely mediated through restored miR-203a-3p expression and subsequent FGF2 pathway inhibition. Thus, CircPVT1 targeting may offer a viable approach to circumvent chemotherapy resistance in melanoma.
- Melanoma
- CircPVT1
- miR 203a 3p
- FGF2
- 5 Fluorouracil
- Apoptosis
- Chemosensitization
- 2026-10-06 (2)
- 2026-10-06 (1)
How to Cite
References
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