Researchers Discover Role of tRNA Fragments in Cancer Progression

A recent study by researchers at Chung-Ang University, South Korea, published in Nature Communications, reveals how a specific transfer RNA-derived fragment, 5′-tRH-GlyGCC, influences cancer progression. The study highlights this molecule’s potential as both a biomarker for early cancer detection and a target for developing new therapies.

5′-tRH-GlyGCC, a small RNA fragment, is produced under cellular stress in the endoplasmic reticulum (ER) by the enzyme IRE1α. This fragment interacts with proteins involved in splicing, a key process in gene regulation, to influence gene expression and support cancer growth. The research demonstrates how this fragment can play a role in alternative splicing, a mechanism often implicated in tumor progression.

IRE1α-mediated cleavage of tRNAGly(GCC) produces 5′-tRH-GlyGCC during ER stress, facilitating cellular adaptation across eukaryotes from yeast to humans. Image credit: Kangseok Lee, Chung-Ang University, Republic of Korea.

The team, led by Professor Kangseok Lee, employed advanced techniques to investigate the role of 5′-tRH-GlyGCC:

• Gene Analysis: Tools like nanopore sequencing were used to study how the fragment affects gene expression.
• Cancer Studies: Laboratory experiments showed how altering the levels of 5′-tRH-GlyGCC impacted cancer cell growth.
• Animal Models: Using mouse models, the researchers demonstrated the therapeutic potential of targeting this RNA fragment.

According to Prof. Lee, the study builds on a serendipitous discovery in 2010, when small RNA fragments like 5′-tRH-GlyGCC were first identified in ovarian cancer samples. “At that time, we didn’t know their significance,” he explained. “This study helps us better understand their role in cancer.”

Key Findings

• Cancer Biomarker: Levels of 5′-tRH-GlyGCC can be measured in blood samples, making it a candidate for early cancer detection.
• Therapeutic Target: Suppressing 5′-tRH-GlyGCC using antisense oligonucleotides (ASOs) in mouse models led to tumor regression, suggesting its potential as a treatment target.

The research highlights how targeting RNA fragments like 5′-tRH-GlyGCC could pave the way for innovative diagnostic and therapeutic approaches. With its potential role in detecting and suppressing cancer growth, 5′-tRH-GlyGCC may contribute to advancements in precision medicine.

Prof. Lee emphasized, “Blocking this RNA fragment showed promising results in mouse models. We are now focusing on methods to translate these findings into human therapies.” This work provides new insight into RNA biology and its connection to cancer, offering a pathway for developing more effective diagnostics and personalized treatments.

Full study in Nature Communications: DOI: 10.1038/s41467-024-53624-4.

Cover photo: Chung-Ang University, College of Pharmacy and R&D Center

Topics: Novel Therapeutics