Objective: This study aims to investigate the role of lncRNA PAPPA-AS1 in platinum-resistant cells of lung adenocarcinoma(LAD) and to explore its possible regulatory mechanism. Methods: The differential expression profiling of lncRNA and mRNA in human lung adenocarcinoma(LAD) parental A549 cells and platinum-resistant cells were detected by RNA-seq; the expression of lncRNA PAPPA-AS1 in A549/DDP and A549/NDP cells were detected by fluorescence quantitative PCR; After using siRNA to down-regulate the expression of PAPPA-AS1 in platinum-resistant lung adenocarcinoma cells, the Chemosensitivity of LAD cells to platinumdrugs was detected by CCK-8 assay;the proliferation ability of platinum-resistant cells was detected by cloning formation assay; flow cytometry was used to detect the apoptosis of platinum-resistant cells; Western blotting was used to detect the expression of Cleaved Caspase-3, Cleaved Caspase-9, p-PI3K, p-Akt and p-mTOR protein levels in A549/DDP and A549/NDP cells. Results: Compared with human LAD parental A549 cells, lncRNA PAPPA-AS1 was highly expressed in A549/DDP and A549/NDP. Compared with the control group, LAD platinum-resistant cells in the si-PAPPA-AS1 group showed increased sensitivity to drugs, decreased cell proliferation, and increased apoptosis (all P<0.05). Compared with the control group, the expression of Cleaved Caspase-3 and Cleaved Caspase-9 protein levels in si-PAPPA-AS1cells were significantly up-regulated, and the expression of phosphorylated PI3K, Akt and mTOR protein levels weredown-regulated. Conclusion: Down-regulation of PAPPA-AS1 can reverse platinumresistance of LAD via inhibiting the PI3K/Akt signaling pathway.

［Key words］lncRNA PAPPA-AS1; platinum resistance; lung cancer; RNA-Seq；cell proliferation; cell apoptosis；PI3K/Akt signaling pathway