ArticleAging2021
Hypoxic pancreatic stellate cell-derived exosomal mirnas promote proliferation and invasion of pancreatic cancer through the PTEN/AKT pathway.
Article in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
- Cancer‑associated fibroblast‑derived extracellular vesicles promote pancreatic cancer progression via the RAP1B/ANLN axis.Oncology reports · 2026Article
- Review
- Exploring the Role of Extracellular Vesicles in Pancreatic and Hepatobiliary Cancers: Advances Through Artificial Intelligence.International journal of molecular sciences · 2026Review
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Extracellular Vesicles in Pancreatic Cancer Function and Potential Clinical Applications.OncoTargets and therapy · 2026Review
- Radiotherapy promotes M2 polarization of macrophages through the regulation of the PTEN/PI3K/AKT signaling pathway through miR-616-3p in lung cancer cell-derived exosomes.In vitro cellular & developmental biology. Animal · 2025Article
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- Decoding the pancreatic cancer microenvironment: The multifaceted regulation of microRNAs.Clinical and translational medicine · 2025Review
- Small extracellular vesicles (sEVs) in pancreatic cancer progression and diagnosis.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- Extracellular vesicles in cancer´s communication: messages we can read and how to answer.Molecular cancer · 2025Review
- Acidity and hypoxia of tumor microenvironment, a positive interplay in extracellular vesicle release by tumor cells.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Advances in the role of extracellular vesicles in circulating microRNA biomarker discovery for lung cancer.Frontiers in cell and developmental biology · 2025Review
- Pancreatic cancer cell- and cancer-associated fibroblast-derived exosomes in disease progression, metastasis, and therapy.Discover oncology · 2024Review
- Pancreatic stellate cells: Key players in pancreatic health and diseases (Review).Molecular medicine reports · 2024Review
- Review
- Molecular profile of metastasis, cell plasticity and EMT in pancreatic cancer: a pre-clinical connection to aggressiveness and drug resistance.Cancer metastasis reviews · 2024Review
- Potential clinical applications of extracellular vesicles in pancreatic cancer: exploring untapped opportunities from biomarkers to novel therapeutic approaches.Extracellular vesicles and circulating nucleic acids · 2024Review
- Exosomes: Emerging Insights into the Progression of Pancreatic Cancer.International journal of biological sciences · 2024Review
- Hypoxia-Driven Changes in Tumor Microenvironment: Insights into Exosome-Mediated Cell Interactions.International journal of nanomedicine · 2024Review
- Role of MicroRNA in Hypoxic Tumours and their Potential as Biomarkers for Early Detection of Cancer.Current molecular medicine · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic stellate cells (PSCs) are important components of the tumor microenvironment in pancreatic cancer (PC) and contribute to its development and metastasis through mechanisms that remain incompletely characterized. Tumor hypoxia affects the function and behavior of PC and stromal cells, and can alter exosomal content to modify cell-cell communication. The present study explored the effects of exosomal miRNAs produced by hypoxia-preconditioned PSCs on the growth and metastatic potential of PC cells. Subcutaneous xenografts and liver metastasis mouse models revealed increased tumorigenic potential upon co-implantation of PC cells and PSCs as compared to PC cells alone. Screening miRNA profiles of mouse plasma exosomes and cultured PSCs, followed by miRNA overexpression and inhibition assays, enabled us to identify miR-4465 and miR-616-3p as prominent hypoxia-induced, PSC-derived, exosomal miRNAs promoting PC cell proliferation, migration, and invasion. Proteomics analysis of PC cells incubated with exosomes derived from hypoxic PSCs showed significant downregulation of PTEN. Dual-luciferase reporter assays and western blotting showed that both miR-4465 and miR-616-3p target PTEN and activate AKT signaling in PC cells. We conclude that hypoxia upregulates miR-4465 and miR-616-3p expression in PSC-derived exosomes. Following exosome uptake, these miRNAs promote PC progression and metastasis by suppressing the PTEN/AKT pathway.
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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.