tRNA-derived small RNA 3’ tRF-Ala CGC obstructs NK cytotoxicity via cleavage of membrane protein MICA in colorectal cancer

作者：Jing Zhang, Chunlin Ou, Xin Li, Li Fu, Qizhi Luo, Jie Wang, Yizhou Zou · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1620550 · 被引用次数：5 · 研究领域：RNA modifications and cancer、Immune Cell Function and Interaction、RNA and protein synthesis mechanisms

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 membr...