ArticleCellular & molecular biology letters2024
Role of microRNA-4739 in enhancing cisplatin chemosensitivity by negative regulation of RHBDD2 in human cervical cancer cells.
Article in Cellular & molecular biology letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 6 citations in OpenAlex.
- MiR-3664-3p through suppressingHeliyon · 2025Article
- Epigenetic modification regulates the ligamentum flavum hypertrophy through miR-335-3p/SERPINE2/β-catenin signaling pathway.Cellular & molecular biology letters · 2025Article
- Matrine Enhances the Antitumor Efficacy of Chidamide in CTCL by Promoting Apoptosis.Recent patents on anti-cancer drug discovery · 2025Article
- The potential role of miR-155 in the tumorigenesis of cervical cancer.Frontiers in cell and developmental biology · 2025Review
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6 authors at 3 institutions in 1 country.
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Abstract
backgroundCisplatin (DDP) is a widely used chemotherapy drug for advanced cervical cancer (CC), but resistance poses a significant challenge. While miR-4739 has been implicated in tumor development, its specific role in regulating DDP resistance in CC remains unclear.
methodsWe analyzed the expression levels of miR-4739 and RHBDD2 in DDP-resistant and DDP-sensitive CC tissues using quantitative real-time polymerase chain reaction (PCR) and assessed their correlation through Spearman's correlation analysis. DDP-resistant CC cell lines (HeLa/DDP and SiHa/DDP) were established by gradually increasing DDP concentrations, followed by transfection with miR-4739 mimics, si-RHBDD2, or a RHBDD2 overexpression vector. A series of functional assays, including CCK-8 assay, colony formation, flow cytometry, and transwell assay were performed. The interaction between miR-4739 and RHBDD2 was confirmed by luciferase reporter assay. We examined the protein levels of RHBDD2, P-gP, MRP1, cleaved caspase-3, and E-cadherin through western blot analysis. Moreover, we generated xenograft tumors by injecting stably transfected HeLa/DDP cells into mice to compare their tumorigenesis capacity.
resultsWe observed downregulation of miR-4739 and upregulation of RHBDD2 in DDP-resistant CC tissues and cell lines. MiR-4739 was shown to directly bind to RHBDD2 gene sequences to repress RHBDD2 expression in HeLa/DDP and SiHa/DDP cells. Our in vitro and in vivo experiments demonstrated that overexpressing miR-4739 overcame DDP resistance in CC cells by targeting RHBDD2. Furthermore, RHBDD2 overexpression reversed the effects of miR-4739 mimics on drug-resistance-related proteins (P-gP and MRP1) and the expression of cleaved caspase-3 and E-cadherin in HeLa/DDP cells.
conclusionsIn summary, our study revealed that miR-4739 can reverse DDP resistance by modulating RHBDD2 in CC cells.
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