Targeting lncRNA PVT1/miR-145-5p/ABCC-1 Pathway Enhances Paclitaxel Sensitivity and Suppresses Melanoma Progression.

Authors

Negar Pedram, Reza Safaralizadeh, Mohammad Ali Hosseinpour Feizi, Dariush Shanehbandi

Published in

International journal of genomics. Volume 2026. Pages 2246468. Epub Oct 06, 2026.

Abstract

As a highly aggressive type of skin cancer, melanoma cells show significant resistance against a variety of chemotherapeutics, such as paclitaxel, which limits the efficacy of the treatment. Studies have highlighted the potential role of noncoding RNA dysregulation in melanoma, affecting tumor progression and drug response, including lncRNA PVT1.
This study investigated whether simultaneous modulation of the lncRNA PVT1/miR-145-5p/ABCC1 axis enhances paclitaxel sensitivity and suppresses malignant behaviors in a melanoma cell line.
Using SK-MEL-3 and A375 cells, we performed PVT1 knockdown using siPVT1, restored miR-145-5p function by transfection, and administered paclitaxel, either alone or in combination. Cell viability was assessed using the MTT assay; apoptosis and cell cycle distribution were analyzed by flow cytometry; and the expression of genes related to apoptosis, cell cycle regulation, migration, and drug resistance was quantified by qRT-PCR.
Combination therapy markedly reduced cell viability compared with single treatments. Cotargeting PVT1 and miR-145-5p significantly enhanced paclitaxel-induced apoptosis, evidenced by increased expression of proapoptotic and downregulation of antiapoptotic genes. The combination also induced a pronounced G1-phase arrest with decreased levels of CDK-4 and CDK-6. Furthermore, gene expression analysis showed downregulation of MMP-9 and ABCC1, along with upregulation of E-cadherin, suggesting reduced migratory potential and reversal of drug resistance.
Simultaneous PVT1 knockdown and miR-145-5p overexpression enhance the anticancer effects of paclitaxel by promoting apoptosis, inducing cell cycle arrest, and mitigating drug resistance in melanoma cells. Targeting the PVT1/miR-145-5p/ABCC1 regulatory network may provide a promising therapeutic strategy to overcome chemoresistance in melanoma.

PMID:
42840833
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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