Highlights

• This is the first study to target NUCKS1 oncogene for CRC treatment using small RNA therapeutics.
• tRF-T36, a tRNA fragment from Chinese yew, is newly identified as a natural RNA molecule that silences NUCKS1 via direct 3′ UTR binding.
• The study introduces tRF-T36 mimic as a promising low-toxicity siRNA drug candidate that remains effective against drug-resistant CRC cells.

Summary

The research article investigates a novel therapeutic approach for colorectal cancer (CRC) by targeting the oncogene NUCKS1 using a plant-derived small RNA fragment.

The researchers identified tRF-T36, a 22-nucleotide fragment from the Chinese yew’s tRNA^Asn(GUU), which binds directly to the 3′ UTR of NUCKS1 mRNA and suppresses its expression via the RNA interference (RNAi) pathway. This suppression leads to inhibition of the PI3K/Akt pathway, a key driver of tumor growth, as confirmed through in vitro experiments and RNA sequencing, and was reversed by activating the pathway with 740Y-P. The tRF-T36 mimic exhibited strong anti-tumor effects in both CRC cell lines and mouse models, including effectiveness in taxol-resistant cells, with minimal toxicity to normal tissues.

These findings present tRF-T36 as the first known siRNA candidate targeting NUCKS1, highlighting its promise as a druggable RNA therapeutic for CRC treatment.

K.-Y. Cao et al., “Targeting NUCKS1 with a fragment of tRNAAsn(GUU) of Chinese yew for the treatment of colorectal cancer,” Non-coding RNA Research, vol. 11, pp. 38–47, Apr. 2025, doi: 10.1016/j.ncrna.2024.11.002.