ArticleJournal of experimental & clinical cancer research : CR2025
Cancer-associated fibroblast promotes tamoxifen resistance in estrogen receptor positive breast cancer via exosomal LncRNA PRKCQ-AS1/miR-200a-3p/MKP1 axis-mediated apoptosis suppression.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- Multi-scale transcriptomic integration reveals LINC00152-high tumor cells promote TGCT progression and T cell exhaustion.British journal of cancer · 2026Article
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- CAFs and Endocrine Therapy Resistance in Hormone Receptor-Positive Breast Cancer.International journal of molecular sciences · 2026Review
- Organoid-Derived Extracellular Vesicles: From Biogenesis and Cargo Mechanisms Toward Therapeutic Applications.International journal of nanomedicine · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTamoxifen resistance remains a significant challenge in the endocrine therapy of estrogen receptor-positive (ER+) breast cancer. Cancer-associated fibroblasts (CAFs) facilitate therapeutic resistance through exosome secretion, yet the role of CAF-derived long non-coding RNAs (lncRNAs) in tamoxifen resistance remains underexplored. This study investigates the mechanism by which CAF-secreted exosomal lncRNA modulates tamoxifen resistance in ER + breast cancer.
methodsCAFs from ER + breast cancer patients and normal fibroblasts (NFs) from healthy control were isolated and cultured ex vivo. Exosomes were extracted from the supernatant of cultured cells using ultracentrifugation. RNA sequencing identified PRKCQ-AS1 as a candidate lncRNA, validated in tamoxifen-sensitive and resistant tumors. Functional assays (qPCR, RNA-seq, dual-luciferase reporter, and in vivo xenografts) elucidated the role of PRKCQ-AS1/miR-200a-3p/MKP1 axis in tamoxifen resistance. Prognostic correlations were assessed in clinical cohorts (n = 471) and TCGA/GEO datasets.
resultsLncRNA PRKCQ-AS1 was markedly upregulated in tamoxifen-resistant tumor samples and was associated with poor prognosis in tamoxifen-treated ER + breast cancer patients but not in those treated with aromatase inhibitors. Exosomal PRKCQ-AS1 derived from CAFs transferred to ER + breast cancer cells, suppressing tamoxifen-induced apoptosis via MKP1 upregulation. Mechanistically, PRKCQ-AS1 acted as a molecular sponge for miR-200a-3p, relieving miR-200a-3p-mediated repression of MKP1. Elevated MKP1 inactivated the MAPK/JNK pathway, attenuating apoptosis. In vivo, PRKCQ-AS1 overexpression accelerated ER + breast tumor growth despite tamoxifen treatment. TGF-β-driven CAF transformation upregulated PAX5, a transcription factor enhancing PRKCQ-AS1 expression.
conclusionsThis study identifies CAF-derived exosomal LncRNA PRKCQ-AS1 as a key mediator of tamoxifen resistance via the miR-200a-3p/MKP1 axis. Targeting this pathway may offer novel therapeutic strategies to overcome endocrine resistance in ER + breast cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.