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Lung cancer remains the leading cause of cancer‐related death worldwide. Previous studies have shown that the novel   KIAA 0247  gene potentially targeted by the tumor suppressor p53 may inhibit the development of several cancers. However, the exact function of   KIAA 0247  in non‐small‐cell lung cancer ( NSCLC ) is unknown. The purpose of the present study was to clarify the role of  KIAA 0247 in  NSCLC .  KIAA 0247 expression was evaluated in tumors and adjacent normal tissues of 197  NSCLC  patients by immunohistochemistry and real‐time  PCR  and analyzed for association with clinicopathological parameters. Results indicated that  KIAA 0247 levels positively correlated with cell differentiation ( P  < .001) and patient survival ( P  < .0001) and negatively correlated with lymph node metastasis ( P  < .001) and advanced p‐ TNM  stage ( P  < .001). In cultured  NSCLC  cell lines,  KIAA 0247 overexpression inhibited cell migration, invasion, and proliferation and downregulated the expression of Jagged1, Notch1 intracellular domain ( NICD ), Snail, cyclin D1, RhoA, RhoC, and  MMP 9, while upregulating that of E‐cadherin and p21. The Notch inhibitor  DAPT  reduced the biological effects of  KIAA 0247 knockdown, suggesting that  KIAA 0247 decreased the carcinogenic activity of  NSCLC  cells through downregulation of Notch signaling. Our results indicate that  KIAA 0247 inhibits  NSCLC  progression by reducing the metastatic potential of cancer cells through downregulation of the Notch pathway, which may underlie the association of  KIAA 0247 expression with favorable clinicopathological characteristics of  NSCLC  patients. These findings suggest that  KIAA 0247 is a candidate prognostic biomarker and potential therapeutic target in  NSCLC .

KIAA 0247 inhibits growth, migration, invasion of non‐small‐cell lung cancer through regulating the Notch pathway