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Translation Reprogramming Caused by tRNA Modifications Represents a New Therapeutic Target for Cancer Treatment
Yan Hu1,2, Ziqi Liu2, Hongke Qu2
1NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Abstract:
Translation reprogramming-induced dysregulation of protein synthesis is a widespread phenomenon in disease progression, especially in tumor cells, where there is abnormally active protein synthesis to support the increasing demands of oncogene expression. This aberrant translation process contributes to various malignant phenotypes of tumors. In the process of protein synthesis, transfer RNAs (tRNAs) transport amino acids to the ribosome according to the codon sequence on mRNA to synthesize the corresponding peptide chain. Thus, tRNAs play a major role in the regulation of translation reprogramming. With the development of sequencing and mass spectrometry technologies, various modifications have been identified in tRNAs. Abnormal tRNA modifications lead to translation reprogramming by affecting the abundance of tRNAs, the cleavage of tRNAs, and the ability of tRNAs to decode mRNAs, thereby promoting the progression of tumors. This review focuses on the mechanisms by which aberrant tRNA modifications contribute to tumorigenesis through translation reprogramming, and provides a comprehensive summary and discussion on the clinical prospects of targeting excessive translation driven by tRNA modifications for cancer therapy. This article is categorized under: Translation > Mechanisms RNA Processing > RNA Editing and Modification.
Insights
Aberrant transfer RNA (tRNA) modifications disrupt protein synthesis, driving tumor growth. Targeting these modified tRNAs offers a promising new avenue for cancer therapy.
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Biology
Background:
- Dysregulated protein synthesis, particularly in cancer cells, supports oncogene expression and malignant phenotypes.
- Transfer RNAs (tRNAs) are crucial for protein synthesis, mediating amino acid transport based on messenger RNA (mRNA) codons.
- Aberrant translation reprogramming, influenced by tRNAs, is a hallmark of disease progression.
Purpose of the Study:
- To review the mechanisms linking abnormal tRNA modifications to tumorigenesis via translation reprogramming.
- To summarize and discuss the clinical potential of targeting tRNA modification-driven translation in cancer therapy.
Main Methods:
- Review of existing literature on tRNA modifications, translation reprogramming, and cancer.
- Analysis of how tRNA abundance, cleavage, and decoding ability are affected by modifications.
- Exploration of clinical strategies targeting aberrant translation in cancer.
Main Results:
- Abnormal tRNA modifications significantly impact tRNA abundance, cleavage, and mRNA decoding.
- These alterations in tRNA function contribute to translation reprogramming and promote tumor progression.
- Specific tRNA modifications are increasingly recognized as drivers of oncogenesis.
Conclusions:
- Aberrant tRNA modifications are key contributors to cancer development through translation reprogramming.
- Targeting the excessive translation driven by tRNA modifications presents a viable therapeutic strategy for cancer treatment.
- Further research into tRNA modification pathways could unveil novel cancer biomarkers and drug targets.
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