Open AccessKIAA 0247 inhibits growth, migration, invasion of non‐small‐cell lung cancer through regulating the Notch pathway
Author(s) -
Xu Yitong,
Ren Hongjiu,
Jiang Jun,
Wang Qiongzi,
Wudu Muli,
Zhang Qingfu,
Su Hongbo,
Wang Chenglong,
Jiang Lihong,
Qiu Xueshan
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13539
Subject(s) - rhoc , downregulation and upregulation , lung cancer , medicine , gene knockdown , cyclin d1 , cancer research , notch signaling pathway , cancer , metastasis , biology , oncology , receptor , cell cycle , cell culture , gene , biochemistry , genetics
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 .