MYBL2 impedes cisplatin sensitivity through suppressing GSDME-mediated pyroptosis in lung adenocarcinoma

The underlying relationship between pyroptosis and tumorigenesis has garnered increasing attention recently. It has been demonstrated that the transcription factor MYB proto-oncogene-like 2 (MYBL2) is elevated in various solid tumors, thereby promoting cell proliferation. However, the role of MYBL2 gene in lung adenocarcinoma (LUAD), especially its potential connection with pyroptosis, is still unclear. Here, by combining ATAC seq and RNA seq methods, we initially identified MYBL2 gene as the main regulatory transcription factor (MR-TF) driving LUAD phenotype plasticity. An in-depth analysis of the sequencing results revealed that the expression of the MYBL2 gene was significantly higher in LUAD tissues than in normal tissues. Further experiments confirmed that MYBL2 promoted the proliferation of LUAD and attenuated tumor cell pyroptosis. Mechanistically, MYBL2 negatively regulated GSDME expression by binding to its promoter, thereby diminishing cisplatin-induced pyroptosis and ultimately leading to reduced chemosensitivity. Moreover, MYBL2 interacted with YAP1 to co-regulate GSDME transcription. The results of this research could be used to inform new strategies for screening effective populations and overcoming treatment resistance, making them potentially clinically valuable.