Background
Lung adenocarcinoma (LUAD) is a pulmonary malignant disease that poses a high risk of mortality and morbidity. Previous study indicated that ORC1 plays an oncogenic function. However, the precise regulatory function that ORC1 serves in the progression of LUAD is still not clearly known.
Conclusion
ORC1 promotes LUAD cell proliferation and inhibits ferroptosis in a SLC7A11-dependent manner. This implies that ORC1 could potentially serve as a useful diagnosis biomarker and treatment target.
Methods
Bioinformatics analyses were performed using TCGA and GEO datasets. The human LUAD cell line NCIH1355, NCIH1568 as well as BEAS-2B cell line (human normal lung epithelial cell) were utilized for in vitro study. LUAD cell proliferation were determined via CCK-8 assays and RT-qPCR for ki-67. The relation of ORC1 and SLC7A11 was detected by Western blot and qPCR with or without sh-RNA. The expression level ACSL4, the biomarker of ferroptosis, were detected using RT-qPCR.
Results
ORC1 and SLC7A11 exhibit high expression levels in both LUAD patients and cell lines, and are strongly associated with poor prognosis. In vitro experiments demonstrate that ORC1 and SLC7A11 promote proliferation of LUAD cell lines while inhibiting gefitinib-induced ferroptosis. Additionally, the function of ORC1 in LUAD cells is dependent on SLC7A11.