tRF-3021a Supports Invasiveness, Apoptosis Resistance, and Global Protein Synthesis in Cancer Cell Lines
Year: 2026
Type: preprint
Abstract: tRNA-derived fragments (tRFs) are relatively recently discovered class of small RNAs implicated in gene-regulatory processes in diverse biological contexts but there have been very few reports of a clear phenotypic role of these small RNAs in cancer progression. By analyzing small RNA-seq data from The Cancer Genome Atlas (TCGA), we found that high expression of three 3' tRFs (tRF-3a), tRF-3009a, tRF-3021a or tRF-3030a, is significantly associated with poor overall survival in low-grade glioma (LGG). In glioblastoma cells, tRF-3009a, tRF-3021a and tRF-3030a enhance cell invasion and migration but tRF-3021a was uniquely required for cell proliferation and suppression of apoptosis. Interestingly, tRF-3021a knockdown decreases global protein synthesis prior to and independent of apoptosis. These data indicate that tRF-3021a supports glioma cell survival and particularly protein synthesis while promoting cellular invasion and migration. Given its association with poor outcome in LGG patients, tRF-3021a represents a promising biomarker and potential therapeutic target in gliomas and these results provide a foundation for future studies to define its molecular interactors and downstream pathways controlling protein synthesis and apoptosis in cancer cells. Implication: tRF-3021a promotes malignant glioma phenotypes, sustains global protein synthesis and prevents spontaneous apoptosis, motivating efforts to evaluate it as a biomarker and therapeutic target.
Authors: Esmaeili Fatemeh, Kumarjeet Banerjee, Ajay Chatrath, Divya Sahu, Yoshiyuki Shibata, Shekhar Saha, Pankaj Kumar, Zhangli Su, Anindya Dutta
Institutions: University of Alabama at Birmingham, University of Virginia
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W7126013040