ArticleThe Journal of clinical investigation2021
Inflammatory cytokine-regulated tRNA-derived fragment tRF-21 suppresses pancreatic ductal adenocarcinoma progression.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 104 citations in OpenAlex.
- tRNA-derived fragment AS-tDR-008272 promotes NSCLC tumorigenesis by propelling glycolytic metabolism via regulating HJURP.Translational oncology · 2026Article
- Integrated genome-wide high-throughput screening and functional validation identifies Sm proteins as essential splicing regulators for gastric cancer progression.Functional & integrative genomics · 2026Article
- RNA splicing in cancer cell death regulation: shedding light on the molecular mechanisms and potential clinical applications.Cell death & disease · 2026Review
- tRNA-Derived Fragment tRF-22 Promotes Immunosuppression by Inhibiting HnRNPAB Ubiquitination in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Harnessing Ribonucleoprotein Granule Biology for Cancer Therapy: The Central Role of Protein Modifications.Research (Washington, D.C.) · 2026Review
- Emerging roles of tsRNAs in programmed cell death and disease therapeutics: challenges, opportunities, and future directions.Non-coding RNA research · 2025Review
- tRF-21LeuTAA Promotes Oxidative Stress by Altering Glutathione Metabolic Enzymes to Support Prostate Cancer Progression.Cancer research · 2025Article
- Identification of plasma tRNA-derived small RNA i-tRF-15:31-Lys-CTT-1 as a biomarker for diagnosis and prognosis of pulmonary arterial hypertension.Non-coding RNA research · 2025Article
- Conserved small RNA networks link inflammation to pain signaling in mice and men.Translational psychiatry · 2025Article
- tRNA-derived fragment tRF-24 drives CELF1 phase separation to promote oncogenic splicing in esophageal squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- A novel protein cPFKFB4 encoded by hsa_circ_0065394 strengthens PKM2-mediated glucose metabolic reprogramming to facilitate pancreatic cancer progression under hypoxia.Molecular cancer · 2025Article
- Mechanisms of Transfer RNA Fragments Functionality Within and Between Cells and Organisms.Cells · 2025Review
- tRF-5004b Enriched Secretory Autophagosomes Induce Endothelial Cell Activation to Drive Acute Respiratory Distress Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The RNA helicase DDX17 enhances androgen receptor stability by interacting with the E3 ubiquitin ligase SPOP in prostate cancer.Translational andrology and urology · 2025Article
- The Roles of tRNA-Derived Fragments in Cancer: Updates and Perspectives.International journal of molecular sciences · 2025Review
- The novel tRNA-derived fragment, tiRNA-Met, inhibits the malignant progression of triple-negative breast cancer by regulating RANBP3L via a targeted interaction with SNRPA.Cellular & molecular biology letters · 2025Article
- tRNA-derived small RNAs in digestive tract diseases: Progress and perspectives.Genes & diseases · 2025Review
- The role of tRNA-Derived small RNAs (tsRNAs) in pancreatic cancer and acute pancreatitis.Non-coding RNA research · 2025Review
- A nuclear tRNA-derived fragment triggers immunity in Arabidopsis.Communications biology · 2025Article
- A novel 5'tRNA-derived fragment tRF-Tyr inhibits tumor progression by targeting hnRNPD in gastric cancer.Cell communication and signaling : CCS · 2025Article
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumorigenic mechanism for pancreatic ductal adenocarcinoma (PDAC) is not clear, although chronic inflammation is implicated. Here, we identified an inflammatory cytokine-regulated transfer RNA-derived (tRNA-derived) fragment, tRF-21-VBY9PYKHD (tRF-21), as a tumor suppressor in PDAC progression. We found that the biogenesis of tRF-21 could be inhibited by leukemia inhibitory factor and IL-6 via the splicing factor SRSF5. Reduced tRF-21 promoted AKT2/1-mediated heterogeneous nuclear ribonucleoprotein L (hnRNP L) phosphorylation, enhancing hnRNP L to interact with dead-box helicase 17 (DDX17) to form an alternative splicing complex. The provoked hnRNP L-DDX17 activity preferentially spliced Caspase 9 and mH2A1 pre-mRNAs to form Caspase 9b and mH2A1.2, promoting PDAC cell malignant phenotypes. The tRF-21 levels were significantly lower in PDACs than in normal tissues, and patients with low tRF-21 levels had a poor prognosis. Treatment of mouse PDAC xenografts or patient-derived xenografts (PDXs) with tRF-21 mimics repressed tumor growth and metastasis. These results demonstrate that tRF-21 has a tumor-suppressive effect and is a potential therapeutic agent for PDAC.
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