ArticleJournal of hematology & oncology2022
CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR.
Article in Journal of hematology & oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
123 citing papers in PubMed, 2 syntheses or guidelines pooled it, 210 citations in OpenAlex.
- Pooled it
- Encapsulation and assessment of therapeutic cargo in engineered exosomes: a systematic review.Journal of nanobiotechnology · 2024Pooled it
- Circulating circRNAs at the frontier of cancer detection, prognosis, and therapy.Chinese medical journal · 2026Review
- CRISPR/Cas9 screen identifies DCAF4 as a novel protector of hepatocellular carcinoma against brachytherapy via stress granule-dependent NRF2 activation.Cell death & disease · 2026Article
- Article
- Review
- Noncoding RNAs are indispensable architects and regulators of biomolecular condensates.Non-coding RNA research · 2026Review
- circOMA1 delivered by exosomes regulates DRD2‑mediated prolactinoma resistance.International journal of molecular medicine · 2026Article
- Decoding the functional network of circular RNAs encoding proteins in hepatocellular carcinoma: from carcinogenesis to clinical transformation.Journal of advanced research · 2026Review
- The Role of Stress Granules in Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026Review
- TRIM26-mediated NKRF degradation drives Osimertinib resistance through SNRPD2-dependent stress granule formation in lung adenocarcinoma.Cell death & disease · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- EIF4A3-induced circUBAC2 promotes lung cancer progression via regulation of the Hippo signaling pathway.Cellular & molecular biology letters · 2026Article
- Circular RNAs in cancer: Its biogenesis, functions, relationships with cancer progression, applications in immunotherapy and biomarker potentials.Cancer immunology, immunotherapy : CII · 2026Review
- The role of circular RNAs as miRNA sponges in the mechanisms and therapeutic potential of triple negative breast cancer.Discover oncology · 2026Review
- The DAG/PKC/CREB1/TGF-β1 axis drives shear-wave elastography stiffness and malignant progression in triple-negative breast cancer via lipid metabolic reprogramming.Cell death & disease · 2026Article
- K48 and K63 linkage-competed ubiquitination of BECN1 promotes circPDE4D-mediated autophagy in chronic obstructive pulmonary disease.Cell death & disease · 2026Article
- Alternative splicing in cancer drug resistance: Mechanisms and therapeutic prospects (Review).Oncology reports · 2026Review
- Long non-coding RNA STMN1P2 promotes breast cancer doxorubicin resistance by inhibiting pyroptosis through the hnRNPU-EZH2-TARF6-MALT1-caspase-1 pathway.Acta pharmacologica Sinica · 2026Article
- Exosomes as Emerging Nanocarriers for Targeted Cancer Therapy.International journal of nanomedicine · 2026Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCircular RNAs (circRNAs) represent a novel type of regulatory RNA characterized by high evolutionary conservation and stability. CircRNAs are expected to be potential diagnostic biomarkers and therapeutic targets for a variety of malignancies. However, the regulatory functions and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) are largely unknown.
methodsBy using RNA high-throughput sequencing technology, qRT-PCR and in situ hybridization assays, we screened dysregulated circRNAs in breast cancer and TNBC tissues. Then in vitro assays, animal models and patient-derived organoids (PDOs) were utilized to explore the roles of the candidate circRNA in TNBC. To investigate the underlying mechanisms, RNA pull-down, RNA immunoprecipitation (RIP), co immunoprecipitation (co-IP) and Western blotting assays were carried out.
resultsIn this study, we demonstrated that circRNA-CREIT was aberrantly downregulated in doxorubicin resistant triple-negative breast cancer (TNBC) cells and associated with a poor prognosis. The RNA binding protein DHX9 was responsible for the reduction in circRNA-CREIT by interacting with the flanking inverted repeat Alu (IRAlu) sequences and inhibiting back-splicing. By utilizing in vitro assays, animal models and patient-derived organoids, we revealed that circRNA-CREIT overexpression significantly enhanced the doxorubicin sensitivity of TNBC cells. Mechanistically, circRNA-CREIT acted as a scaffold to facilitate the interaction between PKR and the E3 ligase HACE1 and promoted proteasomal degradation of PKR protein via K48-linked polyubiquitylation. A reduced PKR/eIF2α signaling axis was identified as a critical downstream effector of circRNA-CREIT, which attenuated the assembly of stress granules (SGs) to activate the RACK1/MTK1 apoptosis signaling pathway. Further investigations revealed that a combination of the SG inhibitor ISRIB and doxorubicin synergistically inhibited TNBC tumor growth. Besides, circRNA-CREIT could be packaged into exosomes and disseminate doxorubicin sensitivity among TNBC cells.
conclusionsOur study demonstrated that targeting circRNA-CREIT and SGs could serve as promising therapeutic strategies against TNBC chemoresistance.
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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.