Highlights

• This research showed that tRNA fragments from non-pathogenic gut E. coli strains have selective anticancer activity against colorectal cancer cells.
• The study identifies EC83, a chemically defined tRF mimic, as a highly potent, structure-dependent RNA therapeutic candidate.
• Gm modification significantly enhances EC83’s cytotoxicity and structural stability, indicating a clear link between RNA chemistry and therapeutic function.

Summary

The research article investigates the antitumor potential of tRNA-derived fragments (tRFs) and tRNA halves from non-pathogenic Escherichia coli (NPECS) strains against colorectal cancer (CRC). It finds that tRF mimics, especially a 22-nucleotide fragment called EC83 derived from tRNA-Leu(CAA), show significant cytotoxicity toward CRC cells, outperforming tRNA halves and even standard chemotherapy (5-FU).

Structural modifications of EC83, particularly 2′-O-methylation of guanosine (Gm), further enhance its cytotoxicity and stability, making the EC83-M2 variant the most effective. These effects are validated both in vitro and in mouse models, with minimal toxicity to normal cells and organs.

The study highlights gut microbiota-derived tRFs as promising, selective RNA-based anticancer agents and encourages further investigation into their therapeutic applications.

K.-Y. Cao, Y. Pan, T.-M. Yan, P. Tao, Y. Xiao, and Z.-H. Jiang, “Antitumor Activities of tRNA-Derived Fragments and tRNA Halves from Non-pathogenic Escherichia coli Strains on Colorectal Cancer and Their Structure-Activity Relationship,” mSystems, vol. 7, no. 2, pp. e00164-22, Apr. 2022, doi: 10.1128/msystems.00164-22.