ArticleFrontiers in immunology2025
tRNA-derived small RNA 3' tRF-Ala CGC obstructs NK cytotoxicity via cleavage of membrane protein MICA in colorectal cancer.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- tRNA-Derived Small RNAs in Digestive Cancers: From Translational Regulation to Immune and Extracellular Communication.Cancer science · 2026Review
- tRNA-derived small RNAs in tumor microenvironment remodeling: From mechanistic insights to therapeutic perspectives.Oncogene · 2026Review
- Biological functions of tsRNAs and research advances in human disease.Biochemistry and biophysics reports · 2026Review
- Transfer RNA expression, modification, and derived small RNAs in cancer biology and clinical potential.Frontiers in immunology · 2026Review
- Association Between Amino Acid Polymorphisms in MICA and MICA-NKG2D Interaction Affinity: Implications and Significance for Tumor Immunity.Biomolecules · 2025Review
- Extracellular vesicles cargo orchestration in colorectal cancer: immune evasion, stromal remodeling, and therapeutic frontiers.Molecular cancer · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Immune escape remains a major challenge in cancer immunotherapy. Transfer RNA (tRNA)-derived small RNA (tsRNA) represents a novel class of non-coding RNAs generated from tRNA cleavage, regulating gene expression at transcriptional and translational levels. These tsRNAs exhibit diverse biological functions, including immune modulation, metabolic disorders, and cell death. Despite their critical involvement in tumor progression, the role of tsRNAs in Natural killer (NK) cells related to immune escape within colorectal cancer (CRC) has not been revealed yet. Methods: High-throughput sequencing and the tRFexplorer database were utilized to compare the profiles of CRC and normal tissues. Techniques such as RT-qPCR, western blotting, and flow cytometry were employed to assess gene and protein expression. The Cell Counting Kit-8 assay, colony formation assay, and apoptosis analysis were used to evaluate tumor heterogeneity. Differential gene expression between the tRF-3021a inhibitor and negative control (NC) in HCT116 cells was quantified and characterized using RNA sequencing. Results: We identified 3' tRF-AlaCGC (tRF-3021a) as significantly upregulated in CRC tissues. Major histocompatibility complex class I related chain A (MICA) is an important and stress-induced ligand of the natural killer group 2 member D receptor (NKG2D) that is expressed in various cancer cells. MICA undergoes post-translational modifications that regulate their expression as they are called membrane-bound MICA (mMICA) at the cancer cell surface. mMICA is a ligand that induces the activation of NK cells. Proteolytic cleavage of mMICA by A Disintegrin Metalloproteinase Domains (ADAMs) is the underlying mechanism in CRC. Mechanistically, tRF-3021a promotes proteolytic cleavage of mMICA by upregulating ADAM10, generating soluble MICA (sMICA). Elevated sMICA acts as a decoy ligand for NKG2D receptors on NK cells, impairing cytotoxicity and facilitating immune escape. Functional assays confirmed that tRF-3021a knockdown enhances NK cell-mediated CRC cell killing, while overexpression promotes CRC proliferation and inhibits apoptosis. Clinically, tRF-3021a is elevated in CRC tissues, serum exosomes, and cell lines, cleaved by ANG, demonstrating diagnostic potential. Conclusion: Our findings reveal tRF-3021a as a novel biomarker and therapeutic target for CRC immunotherapy.
Indexed as
Identifiers
What OpenQuestion holds
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.