ArticleMolecular cancer2013
miR-99b-targeted mTOR induction contributes to irradiation resistance in pancreatic cancer.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 74 citations in OpenAlex.
- PI3K-AKT-FOXO1 pathway targeted by skeletal muscle microRNA to suppress proteolytic gene expression in response to carbohydrate intake during aerobic exercise.Physiological reports · 2018Trial
- mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review).International journal of oncology · 2026Review
- MicroRNA-based strategies to overcome the immunotherapy barrier in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Review
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- Retraction Note: Physcion, a naturally occurring anthraquinone derivative, induces apoptosis and autophagy in human nasopharyngeal carcinoma.Acta pharmacologica Sinica · 2025Article
- Extracellular vesicles derived from mesenchymal stem cells alleviate renal fibrosis via the miR-99b-5p/mTOR/autophagy axis in diabetic kidney disease.Stem cell research & therapy · 2025Article
- Review
- SPACA6-hosted miR-99b~125a~let-7e cluster shapes melanoma resistance by modulating mTOR-mediated immunosuppression.Frontiers in immunology · 2025Article
- Radioresistance-related gene signatures identified by transcriptomics characterize the prognosis and immune landscape of pancreatic cancer patients.BMC cancer · 2024Article
- miRNAs in pancreatic cancer progression and metastasis.Clinical & experimental metastasis · 2024Review
- Epigenetic Regulation of Autophagy in Bone Metabolism.Function (Oxford, England) · 2024Review
- MicroRNAs in pancreatic cancer drug resistance: mechanisms and therapeutic potential.Frontiers in cell and developmental biology · 2024Review
- MicroRNAs: emerging biomarkers and therapeutic targets in pancreatic cancer.Frontiers in molecular biosciences · 2024Review
- LTF Induces Radioresistance by Promoting Autophagy and Forms an AMPK/SP2/NEAT1/miR-214-5p Feedback Loop in Lung Squamous Cell Carcinoma.International journal of biological sciences · 2023Article
- Stabilization of DEPTOR sensitizes hypopharyngeal cancer to radiotherapy via targeting degradation.Molecular therapy oncolytics · 2022Article
- eIF3a regulation of mTOR signaling and translational control via HuR in cellular response to DNA damage.Oncogene · 2022Article
- MicroRNA-mRNA Regulatory Network Mediates Activation of mTOR and VEGF Signaling in African American Prostate Cancer.International journal of molecular sciences · 2022Article
- miR-99b-5p, miR-380-3p, and miR-485-3p are novel chemosensitizing miRNAs in high-risk neuroblastoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Article
- Overexpression of Notch2 enhances radiosensitivity via inhibition of the AKT/mTOR signaling pathway in nasopharyngeal carcinoma.Bioengineered · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRadiation exerts direct antitumor effects and is widely used in clinics, but the efficacy is severely compromised by tumor resistance. Therefore uncovering the mechanism of radioresistance might promote the development of new strategies to overcome radioresistance by manipulating activity of the key molecules.
methodsImmunohistochemistry were used to find whether mTOR were over-activated in radioresistant patients' biopsies. Then Western blot, real-time PCR and transfection were used to find whether radiotherapy regulates the expression and activity of mTOR by modulating its targeting microRNA in human pancreatic cancer cell lines PANC-1, Capan-2 and BxPC-3. Finally efficacy of radiation combined with mTOR dual inhibitor AZD8055 was assessed in vitro and in vivo.
resultsIonizing radiation promoted mTOR expression and activation in pancreatic cancer cells through reducing miR-99b expression, which negatively regulated mTOR. Novel mTOR inhibitor, AZD8055 (10 nM, 100 nM, 500 nM) synergistically promoted radiation (0-10 Gy) induced cell growth inhibition and apoptosis. In human pancreatic cancer xenografts, fractionated radiation combined with AZD8055 treatment further increased the anti-tumor effect, the tumor volume was shrinked to 278 mm3 after combination treatment for 3 weeks compared with single radiation (678 mm3) or AZD8055 (708 mm3) treatment (P < 0.01).
conclusionsOur data provide a rationale for overcoming radio-resistance by combined with mTOR inhibitor AZD8055 in pancreatic cancer therapy.
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