4.7 Article

Pharmacoepitranscriptomic landscape revealing m6A modification could be a drug-effect biomarker for cancer treatment

Journal

MOLECULAR THERAPY-NUCLEIC ACIDS
Volume 28, Issue -, Pages 464-476

Publisher

CELL PRESS
DOI: 10.1016/j.omtn.2022.04.001

Keywords

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Funding

  1. National Natural Science Foundation of China [82073943, 81773823, 81873581]
  2. National Science and Technology Major Project of China [2017ZX09304014]
  3. Natural Science Foundation of Hunan Province [2020JJ4071]
  4. Fundamental Research Funds for the Central Universities of Central South University [1053320192452]

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RNA chemical modifications play a significant role in RNA splicing, transport, stability, and translation. This article focuses on the correlation between these modifications and drug effects, particularly in the context of pharmacogenes. The study reveals the prevalence of chemical modifications, with a specific emphasis on the N6-methyladenosine (m6A) modification. Furthermore, it highlights the close relationship between chemical modifications and anti-tumor drugs, particularly in triple-negative breast cancer, ovarian cancer, and acute myelocytic leukemia.
RNA chemical modifications are a new but rapidly developing field. They can directly affect RNA splicing, transport, stability, and translation. Consequently, they are involved in the occurrence and development of diseases that have been studied extensively in recent years. However, few studies have focused on the correlation between chemical modifications and drug effects. Here, we provide a landscape of six RNA modifications in pharmacogene RNA (pharmacoepitranscriptomics) to fully clarify the correlation between chemical modifications and drugs. We performed systematic and comprehensive analyses on pharmacoepitranscriptomics, including basic characteristics of RNA modification and modification-associated mutations and drugs affected by them. Our results show that chemical modifications are common in pharmacogenes, especially N6-methyladenosine (m6A) modification. In addition, we found a very close relationship between chemical modifications and anti-tumor drugs. More interestingly, the results demonstrate the importance of m6A modification for anti-tumor drugs, especially for drugs in triple-negative breast cancer (TNBC), ovarian cancer, and acute myelocytic leukemia (AML). These results indicate that pharmacoepitranscriptomics could be a new source of drug-effect biomarkers, especially for m6A and anti-tumor drugs.

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