GRWD1 promotes cell proliferation and migration in non-small cell lung cancer by activating the Notch pathway.

GRWD1 is a member of the WD repeat protein family that is over-expressed in various cancer cell lines and associated with poor prognosis in patients with cancer. However, its biological function and mechanism in non-small cell lung cancer (NSCLC) remain unclear. In this study, we aimed to elucidate the role of GRWD1 in NSCLC. Immunohistochemistry on tumor specimens from 170 patients showed that GRWD1 is highly expressed in NSCLC tissues and positively correlated with tumor size, lymph node metastasis, and P-TNM stage, but negatively correlated with differentiation and prognosis. We found that GRWD1 promotes cell colony formation by affecting the expression of Cyclin B1, CDK1, and p27 and inducing G2/M transition. GRWD1 was also found to stimulate cell migration through RhoA, RhoC, and CDC42, and induce epithelial-mesenchymal transition by affecting the expression of E-cadherin, N-cadherin, Vimentin, Snail, Zeb1, and ZO-1. Our results indicated that the GRWD1 can activate the Notch signaling pathway by affecting the Notch intracellular domain and promoting the expression of Hes1. Our use of DAPT to suppress Notch signaling confirmed that GRWD1 promotes the progression of NSCLC through the Notch signaling pathway and may be a potential prognostic biomarker and therapeutic target for this disease.

Wang Q ，Ren H ，Xu Y ，Jiang J ，Wudu M ，Liu Z ，Su H ，Jiang X ，Zhang Y ，Zhang B ，Qiu X ... -  《-》

GRWD1 Over-Expression Promotes Gastric Cancer Progression by Activating Notch Signaling Pathway via Up-Regulation of ADAM17.

Ding H ，Feng Z ，Hu K 《-》

Novel long non-coding RNA LBX2-AS1 indicates poor prognosis and promotes cell proliferation and metastasis through Notch signaling in non-small cell lung cancer.

Tang LX ，Su SF ，Wan Q ，He P ，Xhang Y ，Cheng XM ... -  《-》

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

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.

Xu Y ，Ren H ，Jiang J ，Wang Q ，Wudu M ，Zhang Q ，Su H ，Wang C ，Jiang L ，Qiu X ... -  《-》

Overexpression of RNF187 induces cell EMT and apoptosis resistance in NSCLC.

Overexpression of RING finger protein 187 (RNF187) was recently revealed to be a driver of several cancers. However, the expression and function of RNF187 in non-small-cell lung cancer (NSCLC) are still unknown. Here, we uncovered that RNF187 expression was significantly higher in NSCLC samples than in matched normal lung samples at both the messenger RNA (3.55 ± 0.79 vs. 1.74 ± 0.63) and protein (2.85 ± 0.14 vs. 1.24 ± 0.02) levels. By downregulating or upregulating RNF187 expression in NSCLC cells, we showed that elevated RNF187 expression distinctly enhanced the migration, invasion, and colony formation of NSCLC cells. Moreover, we revealed that high level of RNF187 promoted NSCLC progression by inducing cell epithelial to mesenchymal transition (EMT) and apoptosis resistance mainly via activating the mitogen-activated protein kinase and PI3K signaling. Clinically, we demonstrated that RNF187 expression was positively associated with advanced TNM stage (p = 1.29 × 10 -6 ), lymph node metastasis ( p = 2.69 × 10 -9 ), and large tumor size ( p = 0.002). Importantly, NSCLC patients with elevated RNF187 expression related to the short overall survival rate( p = 1.29, E-7) and could serve as an independent prognostic factor in NSCLC patients. Thus, elevated RNF187 expression promotes NSCLC development by inducing cell EMT and apoptosis resistance, and RNF187 may be a novel prognostic indicator for NSCLC patients after curative resection.

Fu Z ，Yu W ，Wang H ，Chen X ... -  《-》