Evidence map›Paper›PMID 40227561›Full record

ArticleCell biochemistry and biophysics2025

Morphine Contributes to Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells by Blocking COX-2 Methylation via Regulating the miR-23a-3p/DNMT3A Feedback.

Jian Cui, Nina Ma, Xiaohui Li, Xuexin Chen, Junxia Zhang, Wenjuan Zhang, Hong Li

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Article in Cell biochemistry and biophysics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Jian CuiDepartment of Anaesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Province, China.
Nina MaDepartment of Anaesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Province, China.
Xiaohui LiDepartment of Anaesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Province, China.
Xuexin ChenDepartment of Anaesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Province, China.
Junxia ZhangNingxia Medical University, Yinchuan, Ningxia Province, China.
Wenjuan ZhangNingxia Medical University, Yinchuan, Ningxia Province, China.
Hong LiDepartment of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Province, China. lexingran@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To investigate the effects and mechanisms of morphine on epithelial-mesenchymal transformation (EMT) in triple-negative breast cancer (TNBC). The levels of miR-23a-3p, DNMT3A, and COX-2 in tumor tissues from metastatic TNBC patients treated with morphine were assessed using qRT-PCR. Functional assays assessed morphine's impact on TNBC cell malignancy. Dual luciferase reporter and RNA pull-down assays investigated the interaction between miR-23a-3p and DNMT3A. miR-23a-3p inhibitor and DNMT3A siRNA were transfected into TNBC cells. Protein expression was analyzed by Western blot. Methylation status of miR-23a-3p and COX-2 was assessed via methylation-specific PCR. Rescue experiments were performed to research whether morphine modulates EMT in TNBC through COX-2 methylation regulation via the miR-23a-3p/DNMT3A feedback loop. The effects of morphine on TNBC in nude mice xenotransplantation were studied. In metastatic TNBC patients treated with morphine, miR-23a-3p and COX-2 expression were elevated, and DNMT3A levels were reduced. In TNBC cells, morphine enhanced migration, invasion, and EMT, and suppressed apoptosis. It upregulated miR-23a-3p and COX-2; downregulated DNMT3A; and inhibited methylation of miR-23a-3p and COX-2. miR-23a-3p directly inhibited DNMT3A expression. In morphine-treated TNBC cells, silencing DNMT3A reduced methylation of miR-23a-3p and COX-2. miR-23a-3p inhibitor suppressed migration, invasion, and EMT, and promoted apoptosis; however, these effects were reversed by DNMT3A silencing. In vivo, morphine promoted tumor EMT and metastasis in TNBC; reduced miR-23a-3p and COX-2 methylation; and decreased DNMT3A expression. Morphine accelerated EMT in TNBC by inhibiting COX-2 methylation through the miR-23a-3p/DNMT3A loop.

Indexed as

Cyclooxygenase 2DNA (Cytosine-5-)-MethyltransferasesEpithelial-Mesenchymal TransitionFeedback, PhysiologicalMicroRNAsMorphineTriple Negative Breast NeoplasmsAnimalsCell Line, TumorCell MovementDNA MethylationDNA Methyltransferase 3AFemaleGene Expression Regulation, NeoplasticHumansMiceCyclooxygenase 2DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanMicroRNAsMIRN23a microRNA, humanMorphineCOX-2 methylationEMTmiR-23a-3p/DNMT3AMorphineTNBC

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.