A new approach to lung cancer treatment: Targeting endoplasmic reticulum stress

Endoplasmic reticulum stress plays a pivotal role in responding to external stimuli, which is closely involved in cancer cell survival. However, its upstream regulatory mechanism has not been well elucidated. Previously we have reported that the methyltransferase like protein METTL7B promoted lung adenocarcinoma progression and TKI resistance mainly via its regulation of ROS metabolism, which may related to its mRNA methylation function. However, whether METTL7B could work as a mRNA methylator remains not clear. Our latest data indicated that the expression of METTL7B in LUAD cell lines was significantly negatively correlated with GRP78, IRE1 and XBP-1s, which are key signaling cohort in endoplasmic reticulum stress and the sensitivity of cells to anticancer drugs. On the other hand, METTL7B can up-regulate the mRNA methylation level and reduce the mRNA stability of GRP78, IRE1 and XBP-1s. Moreover, we also identify Proflavine Hemisulfate, a clinically used preservative agent, as a novel METTL7B inhibitor that potently suppresses its m⁶A methyltransferase activity and inhibit the proliferation of lung adenocarcinoma cells in a dose-dependent manner. These findings provide a scientific basis for elucidating the RNA methyltransferase activity of METTL7B and new therapeutic target for lung adenocarcinoma.