[Sportschosun Jang Jong-ho reporter] A study has found that the EZH1 Q571R mutation, commonly seen in thyroid cancer, blocks the expression of key tumor suppressor genes and promotes cancer cell growth. The mutation's ability to condense chromatin was identified as a key driver of cancer progression.
As of 2023, the number of people living with thyroid cancer in South Korea stood at about 587,000, accounting for 21.5% of all cancer patients and representing the highest share among cancer types in the country. The EZH1 Q571R mutation, a variant of the EZH1 protein that suppresses gene expression, has often been found in patients with follicular and oncocytic thyroid cancer, but its impact on cancer onset and progression has not been sufficiently studied.
Against this backdrop, a joint research team led by Lee Cheol-hwan of the Department of Pharmacology at Seoul National University College of Medicine, Lee Gyu-eon of Breast and Endocrine Surgery at Seoul National University Hospital, and Ryu Je-gyeong of the Department of Physics and Astronomy at Seoul National University, along with students Kim Han-byeol, Kim Do-gyun and Ha Seong-yun, clarified the mechanism of the EZH1 Q571R mutation using thyroid cancer patient tissue and cell lines. The cell lines were engineered to continue dividing and growing in culture without dying.
Biochemical, single-molecule and epigenomic analyses showed that the EZH1 Q571R mutation increases enzyme activity and chromatin condensation ability. As a result, repressive histone marks expanded into regions marked by activating histone marks, and the two marks were found to coexist abnormally. This blocked the expression of major tumor suppressor genes and promoted cancer growth.
These findings were consistently observed in actual patient tissue and in animal experiments. In patient tissue carrying the EZH1 Q571R mutation, the expression of tumor suppressor genes was reduced. In animal tests, the mutation promoted cancer growth by about 34% compared with the wild type.
The team also conducted a self-pulldown analysis to determine why mutations in EZH2, a homologous protein of EZH1, are not found in thyroid cancer. The results showed that although the EZH2 Q570R mutation increased enzyme activity, its chromatin condensation ability was low, making the risk of cancer development smaller. The researchers explained that chromatin condensation ability is the key factor in cancer growth.
Lee Cheol-hwan, professor in the Department of Pharmacology at Seoul National University College of Medicine, said, "The greatest significance of this study is that we were able to explain the function of the EZH1 Q571R mutation at the molecular level. We will expand our research in the future toward treatment strategies that target the biological mechanisms of epigenetic mutations."
Lee Gyu-eon, professor of Breast and Endocrine Surgery at Seoul National University Hospital, emphasized, "Through this study, we confirmed that the EZH1 Q571R mutation blocks tumor suppressor gene expression and promotes cancer growth. It is meaningful that we identified chromatin condensation ability as the key factor behind this process."
Ryu Je-gyeong, professor in the Department of Physics and Astronomy at Seoul National University, said, "It is a significant achievement that we were the first to show, through a single-molecule biophysical approach that combines medicine, biology, omics and physics, that the EZH1 Q571R mutation enhances chromatin condensation."
Meanwhile, the study was published in the latest issue of the international journal Molecular Cell (IF 16.0).
Jang Jong-ho, reporter bellho@sportschosun.com
This article has been translated by GripLabs Mingo AI.
