DNA and protein methyltransferases inhibition by adenosine dialdehyde reduces the proliferation and migration of breast and lung cancer cells by downregulating autophagy

Abstract

Protein and DNA methylation is involved in various biological functions such as signal transmission, DNA repair, and gene expression. Abnormal regulation of methyltransferases has been linked to multiple types of cancer, but its link to autophagy and carcinogenesis in breast and lung cancer is not fully understood. We utilized UALCAN, a web tool, to investigate breast and lung cancer database from The Cancer Genome Atlas. We found that 17 methyltransferases are upregulated in breast and/or lung cancer. We investigated the effect of methylation inhibition on two breast cancer cell lines (MDA-MB-231 and MCF-7) and two lung cancer cell lines (H292 and A549) by treating them with the indirect methyltransferase inhibitor adenosine dialdehyde (AdOx). We found that the migration ability of all cell lines was decreased, and the growth rate of MDA-MB-231, MCF-7 and H292 was also decreased after AdOx treatment. These results were correlated with an inhibition of the autophagy in MDA-MB-231, MCF-7 and H292 cell lines, since AdOx treatment induced a decreased expression of ATG7, a reduced ratio LC3-II/LC3-I and an increased p62 level. These findings suggest that inhibiting cells’ methylation ability could be a potential target for breast and lung cancer treatment.

Global research and emerging trends in autophagy in lung cancer: a bibliometric and visualized study from 2013 to 2022

“…Various genes and signaling pathways, such as PARP1-mediated AMPK-mTOR, RPL11, COTE-1, PINK1, PEDF, and MALAT1, have been identified to play critical roles in regulating autophagy and influencing lung cancer cell proliferation, migration, and invasion ( Ma et al, 2018 ; Lu et al, 2020 ; Miao et al, 2022 ; Chen et al, 2023 ; Ma et al, 2023 ; Zhang et al, 2023 ). Additionally, certain compounds, such as the metal, Cd, schizandrin A, pinocembrin, adenine aldehyde, and inhibitors of basal autophagy, have been found to induce autophagy in lung cancer cells, affecting proliferation and migration ( Kaminskyy et al, 2012 ; Wang et al, 2020 ; Gong, 2021 ; Zhu et al, 2021 ; Ghemrawi et al, 2023 ).…”

PMTPred: Machine Learning Based Prediction of Protein Methyltransferases using the Composition of k-spaced Amino Acid Pairs

“…Growing evidence supports that, PMTs have been correlated with a variety of human malignancies. Nowadays, PMTs are a promising target class for therapeutic intervention in cancer [9, 75]. Thus, we have developed a machine-learning-based method for the prediction of PMTs called PMTPred.…”