Organoid transcriptomics identifies IFIT-associated immune modulation during cryptotanshinone treatment for cancer
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Abstract
Abstract Bladder cancer (BC), particularly muscle-invasive and metastatic disease, remains a major clinical challenge despite recent advances in immunotherapy. In this study, we aimed to identify a promising antitumor compound from five candidate small molecules and to explore its potential roles in BC progression. Through antiproliferative screening, cryptotanshinone (CTS) was identified as the promising candidate. Using both two-dimensional BC cell lines and three-dimensional bladder tumor organoid models, we comprehensively evaluated the effects of CTS on cell proliferation, migration, apoptosis, and organoid growth. To further explore the underlying mechanisms, transcriptomic sequencing based on bladder cancer organoid models, protein-protein interaction network analysis, and public databases (TCGA-BLCA, TIMER, and TISIDB) were integrated to examine immune-related pathways and potential molecular targets associated with CTS. GeneMANIA network prediction and molecular docking analyses were subsequently performed to investigate upstream regulatory networks and the potential interactions between CTS and key components of the cGAS-STING-IFN-I-JAK-STAT signaling pathway. Integrative analyses suggested that IFIT1, IFIT2, and IFIT3 may function as immune-associated genes potentially linked to BC progression, patient prognosis, immune cell infiltration, and PD-1/PD-L1 expression. Molecular docking results suggested that CTS may interact with core regulatory proteins within the cGAS-STING-IFN-I-JAK-STAT pathway, potentially influencing IFIT transcriptional regulation. Collectively, these findings indicate that CTS exhibits measurable antitumor and immunomodulatory effects, which may be associated with modulation of the cGAS-STING-IFN-I-JAK-STAT-IFIT signaling axis, supporting its potential as a small-molecule candidate for bladder cancer.
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- Authors
- Yang, M., Li, S., Li, R., Dong, Y., Zhou, M., Zhao, J., Liu, M., & Tan, R.
- Affiliations
- Chengdu University of Traditional Chinese Medicine (CN)
- Zhongnan Hospital of Wuhan University (CN)
- University of Electronic Science and Technology of China (CN)
- Sichuan Academy of Traditional Chinese Medicine (CN)
- National Center for Nanoscience and Technology (CN)
- Brigham and Women's Hospital (US)
- Corresponding author
- Zhao, Junning
- Liu, Miao
- Tan, Ruirong
- ORCID
- Liu, Miao
- Venue
- New Biotechnology
- Publisher
- Elsevier BV
- Published
- 2026-09
- Volume
- 94
- Pages
- 66-82
- ISSN
- 1871-6784 (ISSN-L)
- OpenAlex
- W7161157154
- Cited by
- 0
- References
- 80
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- New Biotechnology (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82204695)
- Topics
- Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- cryptotanshinone, bladder cancer, IFIT1, IFIT2, IFIT3, interferon-stimulated genes, interferon signaling, TBK1 phosphorylation, STAT1 phosphorylation, immunomodulation, PD-1/PD-L1, small molecule anticancer agents, tumor immune infiltration, apoptosis
- MeSH terms
- Urinary Bladder Neoplasms, Cell Movement, Humans, Phenanthrenes, Gene Expression Regulation, Neoplastic, RNA-Binding Proteins, Apoptosis, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Cell Proliferation, Apoptosis Regulatory Proteins, Transcriptome, Molecular Docking Simulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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