Lung cancer is one of the most common
malignancies and the leading cause of
cancer-related death in the world. In patients with advanced
lung adenocarcinoma who are negative for driver gene mutations,
platinum-based
chemotherapy represented by
cisplatin remain the standard of care. Therefore, studying the mechanism behind inevitable
cisplatin resistance in
lung adenocarcinoma is still important. In this study, the potentially related differential expression gene for
cisplatin resistance in
lung adenocarcinoma was screened in the GEO database. The expression level of HEY1 in cell lines of
lung adenocarcinoma was detected and HEY1 expression was up-regulated in
cisplatin-resistant
lung adenocarcinoma tissues and cell lines A549/DDP. Patients with high HEY1 expression have poor prognosis after
cisplatin therapy. Gain and loss function assays uncovered that HEY1 could regulate the
cisplatin sensitivity of NSCLC cells. In vivo experiments have confirmed that silence of HEY1 expression can induce
cisplatin resistance, and epithelial-mesenchymal transition (EMT) changes occur during this process. Mechanically, HEY1 silencing significantly up-regulated
E-cadherin expression and down-regulated
Vimentin in A549/DDP cells. While up-regulation of HEY1 resulted in down-regulation of
E-cadherin and up-regulation of
Vimentin in A549 cells. Immunohistochemical experiments confirmed that
E-cadherin was significantly decreased, and
Vimentin expression was significantly up-regulated in
cisplatin-resistant
lung adenocarcinoma tissues. HEY1 can mediate the occurrence of
cisplatin-acquired resistance in
lung adenocarcinoma, and the possible mechanism is to regulate the EMT. The results of this study can provide a new direction and target for clinical research on the reversal of
cisplatin resistance in
lung adenocarcinoma.