Journal
TOXICOLOGY IN VITRO
Volume 70, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2020.105037
Keywords
Histone methylation; EMT; Radiation; Histone methyltransferases (G9a)
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Funding
- Science and Engineering Research Board, Department of Science and Technology, Government of India [YSS/2014/000518]
- Department of Science and Technology, New Delhi [SL/P-12/2016]
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This study investigated the role of histone methyltransferase G9a in radiation-induced EMT signaling, finding that G9a inhibitor can inhibit radiation-induced EMT and ROS generation, as well as affect the expression of the E-cadherin promoter.
Lung cancer patients who have undergone radiotherapy developed severe complications such as pneumonitis and fibrosis. Upon irradiation, epithelial cells acquire mesenchymal phenotype via a process called epithelial to mesenchymal transition (EMT), which plays a vital role in organ fibrosis. Several mechanisms have been studied on EMT, however, the correlation between radiation-induced EMT and epigenetic changes are not well known. In the present study, we investigated the role of histone methyltransferase G9a on radiation-induced EMT signaling. There was an increase in total global histone methylation level in irradiated epithelial cells. Western blot analysis on irradiated cells showed an increased expression of H3K9me2/3. The pre-treatment of G9a inhibitor enhanced E-cadherin expression and decreased the mesenchymal markers like N-cadherin, vimentin in the radiated group. Surprisingly, radiation-induced ROS generation and pERK1/2 levels were also inhibited by G9a inhibitor BIX01294, which is showing its antioxidant potential. The ChIP-qPCR analysis on the E-cadherin promoter suggested that G9a and Snail might have formed complex to enrich suppressive marker H3K9me2/3. On the whole, our present study suggested that 1] ROS could modify H3K9 methylation via G9a and promote radiationinduced lung EMT in Beas2B and A549 cells 2] E-cadherin promoter enrichment with heterochromatin mark H3K9me2 expression upon irradiation could be modified by regulating G9a methyltransferase.
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