Abstract:

Objective Lung cancer has become one of the main causes of cancer death. Currently，the therapeutic effect of various kinds of lung cancer is limited. It is urgent to continue exploring potential therapeutic targets for lung cancer. This study is to investigate the function and mechanism of ADGRD1 in non⁃small cell lung cancer（NSCLC）. Methods Analyzing the expression level of ADGRD1 in NSCLC tissues through The Cancer Genome Atlas（TCGA）database，and the relationship between ADGRD1 expression and the prognosis of NSCLC patients. Quantitative polymerase chain reaction（qPCR）was used to detect the expression of ADGRD1 in lung cancer and its adjacent normal tissues. After ADGRD1 overexpression or knockdown in different lung cancer Cell lines，CCK⁃8（Cell Counting Kit⁃8）and cell clone formation assay were used to observe the effect of ADGRD1 on the proliferation of NSCLC cells. Meanwhile，cell migration assay was used to observe the effect of ADGRD1 on the migration of NSCLC cells. The downstream pathway was detected by western blot to explore the potential mecha⁃ nism of ADGRD1. Results TCGA database analysis found that the expression of ADGRD1 in lung cancer tissues was significantly lower than that in adjacent normal tissues（P < 0.05），and decreased ADGRD1 expression was associated with poor prognosis（P < 0.01）. The results of qPCR detection of 20 clinical samples showed that the ADGRD1 mRNA level decreased in lung tumor compared with its adjacent normal tissues（0.56 ± 0.16 vs. 1.00 ± 0.22，P < 0.01）. ADGRD1 Overexpression in A549 and H1299 cells significantly inhibited cell proliferation（P < 0.001）and migration（P < 0.01），while knockdown of ADGRD1 in H1975 cells significantly promoted cell prolif⁃eration（P < 0.01）and migration（P < 0.001）. The study of functional mechanism shows that ADGRD1 may be closely related to the proliferation and metastasis of lung cancer cells through the AKT⁃mTOR pathway. Conclusions ADGRD1 significantly inhibits the proliferation and metastasis of NSCLC，which may be a novel prognostic diagnostic and therapeutic target of NSCLC.

Key words:

ADGRD1, non?small cell lung cancer, proliferation, metastasis