ArticleThe Kaohsiung journal of medical sciences2022
Cancer-associated fibroblast-secreted miR-421 promotes pancreatic cancer by regulating the SIRT3/H3K9Ac/HIF-1α axis.
Article in The Kaohsiung journal of medical sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- Dual role of exosomes in pancreatic cancer: Underlying mechanisms and research advances (Review).Oncology letters · 2026Review
- Review
- The histone acylation network: emerging therapeutic targets for remodeling the epigenetic landscape in pancreatic ductal adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- The possible role of sirtuins and MiRNAs in gastrointestinal cancers: special focus on Sirt1.Cancer cell international · 2026Review
- Role of cancer-associated fibroblast-derived exosomes in pancreatic cancer: clinical therapeutic potential and targeting challenges.Frontiers in immunology · 2026Review
- Identification and Preliminary mRNA Validation of Key Genes Associated with Tolerogenic Dendritic Cells in Keloid Based on Transcriptome Data.Clinical, cosmetic and investigational dermatology · 2026Article
- Effects of residual PAH exposure from firefighters' skin and turnout gear on biospecimen microRNA expression.Environmental research · 2025Article
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- Significance of Epigenetic Alteration in Cancer-Associated Fibroblasts on the Development of Carcinoma.International journal of molecular sciences · 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
- Regulation of cancer-associated fibroblasts for enhanced cancer immunotherapy using advanced functional nanomedicines: an updated review.Journal of nanobiotechnology · 2025Review
- Sirtuins as Key Regulators in Pancreatic Cancer: Insights into Signaling Mechanisms and Therapeutic Implications.Cancers · 2024Review
- The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering.Cell communication and signaling : CCS · 2024Review
- Pancreatic cancer cell- and cancer-associated fibroblast-derived exosomes in disease progression, metastasis, and therapy.Discover oncology · 2024Review
- The strict regulation of HIF-1α by non-coding RNAs: new insight towards proliferation, metastasis, and therapeutic resistance strategies.Cancer metastasis reviews · 2024Review
- Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via exosomes in gastrointestinal tumors.Frontiers in oncology · 2024Review
- Downregulated antisense lncRNAAmerican journal of cancer research · 2024Article
- The hidden messengers: cancer associated fibroblasts-derived exosomal miRNAs as key regulators of cancer malignancy.Frontiers in cell and developmental biology · 2024Review
- Targeting sirtuins for cancer therapy: epigenetics modifications and beyond.Theranostics · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
This study was designed to explore the effects of exosomal miR-421 secreted by cancer-associated fibroblasts (CAFs) on pancreatic cancer (PC) progression and the mechanisms involved. CAFs and exosomes (exos) were isolated and identified. PC cells were treated with CAF-derived exos (CAF-exos). Western blotting and quantitative polymerase chain reaction (qPCR) were used to measure miR-421, sirtuin-3 (SIRT3), and hypoxia duciblefactors-1 alpha (HIF-1α) levels. Cell counting kit-8 (CCK-8), wound-healing, and transwell migration assays were used to measure proliferation, migration, and invasion abilities of the cells. Dual-luciferase assay and RNA immunoprecipitation (RIP) experiment analyzed the relationship between miR-421 and SIRT3. Chromatin immunoprecipitation (f)-verified H3K9Ac enrichment in the HIF-1α promoter region. In vivo tumorigenesis experiments were performed to further explore the effects of exosomal miR-421 from CAFs on PC. CAFs and exos were successfully isolated. CAF-exo-treated PC cells highly expressed miR-421 and had increased cell proliferation, migration, and invasion abilities. Knocking down miR-421 increased the expression of SIRT3. SIRT3 is a target of miR-421, and inhibiting the expression of SIRT3 reversed the negative effects of miR-421 knockdown on PC cell. Knocking down miR-421 in CAF-exo inhibited the expression of HIF-1α in PC cells. Moreover, SIRT3-mediated HIF-1α expression by regulating H3K9Ac. HIF-1α overexpression reversed the inhibiting effects of SIRT3 overexpression on PC progression and counteracted the inhibiting effects of miR-421 knockdown on glycolysis. Moreover, in vivo tumorigenesis experiments showed that knocking down miR-421 attenuated CAF-exo induced tumor growth. Exosomal miR-421 from CAFs promoted PC progression by regulating the SIRT3/H3K9Ac/HIF-1α axis. This study provided insights into the molecular mechanism of PC.
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