KIAA0247 inhibits growth, migration, invasion of non‐small‐cell lung cancer through regulating the Notch pathway

Abstract

Lung cancer remains the leading cause of cancer‐related death worldwide. Previous studies have shown that the novel KIAA0247 gene potentially targeted by the tumor suppressor p53 may inhibit the development of several cancers. However, the exact function of KIAA0247 in non‐small‐cell lung cancer (NSCLC) is unknown. The purpose of the present study was to clarify the role of KIAA0247 in NSCLC. KIAA0247 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 KIAA0247 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, KIAA0247 overexpression inhibited cell migration, invasion, and proliferation and downregulated the expression of Jagged1, Notch1 intracellular domain (NICD), Snail, cyclin D1, RhoA, RhoC, and MMP9, while upregulating that of E‐cadherin and p21. The Notch inhibitor DAPT reduced the biological effects of KIAA0247 knockdown, suggesting that KIAA0247 decreased the carcinogenic activity of NSCLC cells through downregulation of Notch signaling. Our results indicate that KIAA0247 inhibits NSCLC progression by reducing the metastatic potential of cancer cells through downregulation of the Notch pathway, which may underlie the association of KIAA0247 expression with favorable clinicopathological characteristics of NSCLC patients. These findings suggest that KIAA0247 is a candidate prognostic biomarker and potential therapeutic target in NSCLC.

MicroRNA-582-5p suppresses non-small cell lung cancer cells growth and invasion via downregulating NOTCH1

“…Licciulli et al[30] found that NOTCH1 function was required for the initiation of lung adenocarcinoma, belonging to the histopathologic class of NSCLC, and controlled tumor cell survival via suppression of p53-mediated apoptosis through the regulation of p53 stability. Recent study by Xu et al showed that KIAA0247 restrained NSCLC progression through attenuating proliferation, migration and invasion of cancer cells through inhibition of the NOTCH pathway[31]. Clinically oriented studies have highlighted that NOTCH signaling impacts survival in lung cancer patients.…”

MKRN2 inhibits migration and invasion of non-small-cell lung cancer by negatively regulating the PI3K/Akt pathway

“…HBE cells were cultured in Dulbecco’s modified Eagle medium (DMEM) with high glucose; A549, H1299, H460, H226, and H292 cells were cultured in Roswell Park Memorial Institute 1640 medium; and SK-MES-1 cells were cultured in MEM medium. Cells were maintained in a 5% CO 2 incubator at 37°C [ 27 ].…”

Astrocyte Elevated Gene 1 (AEG-1) Acts as a Promoter Gene in Clear Cell Renal Cell Carcinoma Cell Growth and Metastasis

“…A wound was scratched using a 100-μl pipette tip. The gap was photographed at 0 h and 24 h [16]. The invasion of Caki-2 cells was detected using a BioCoat™ Matrigel-coated Invasion Chamber (8.0-μm membrane, BD Biosciences, USA).…”