A novel mechanism driving poor-prognostic gastric cancer: overexpression of the transcription factor Krüppel-like factor 16 promotes growth and metastasis of gastric cancer through regulating the Notch pathway.

Gastric cancer (GC) is one of the most common malignant tumors worldwide and has high rates of morbidity and mortality. This study investigated the role of Krüppel-like factor 16 (KLF16) in GC. Real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to examine the expression of KLF16 in gastric cells and tissues. Gene overexpression and silencing were applied to study the involvement of KLF16 in GC cell growth and metastasis along with its underlying mechanism. The results indicate that KLF16 overexpression is significantly associated with nodal status, distant metastasis, staging, degree of differentiation, vascular invasion, and patient survival. Multivariate Cox proportional hazards regression model analysis revealed that the overexpression of KLF16 is an independent prognostic biomarker of GC. The in vitro study revealed that up-regulated KLF16 accelerates cell growth and metastasis, whereas the inhibition of KLF16 suppresses these cellular activities. The results of an animal study also indicated that the overexpression and silencing of KLF16 accelerate and repress xenograft proliferation and metastasis. Further studies of affected cell growth and metastasis revealed that KLF16 modulates the cell cycle and epithelial-mesenchymal transition through transcriptional regulation of microfibrillar-associated protein 5. Collectively, these results reveal that KLF16 overexpression is a potential prognostic biomarker and therapeutic target for the treatment of GC.

Aberrant Expression of NCAPG is Associated with Prognosis and Progression of Gastric Cancer.

INTRODUCTION: Gastric cancer (GC), one of the most prevalent malignancies, is the third-leading cause of cancer-related deaths globally. The aim of this study is to investigate the involvement of non-structural maintenance of chromosomes condensin I complex subunit G (NCAPG) in the prognosis of GC. METHODS: Western blotting and immunostaining were employed to measure the NCAPG level in gastric tissues and cells. Kaplan-Meier analysis was applied to analyze the prognostic value of NCAPG in GC. RNA interference was applied to investigate the influence of the NCAPG silencing on GC cell growth and spread. RESULTS: NCAPG overexpression was associated with several clinicopathologic characteristics, including nodal status (P = 0.0378), distant metastasis (P = 0.0088), staging (P = 0.0230), vascular invasion (P = 0.0012), and disease-free survival (P = 0.004). Kaplan-Meier analysis revealed that NCAPG overexpression was positively correlated to poor GC patients disease-free and overall survival (P = 0.004 and P < 0.001, respectively). Univariate Cox regression analysis showed that the overexpression of NCAPG was a prognostic biomarker of GC (P = 0.005). In cultured GC cells, the knockdown of NCAPG suppressed cell proliferation, migration and invasion. Meanwhile, further studies revealed that the NCAPG silencing induces the G0/G1 cell cycle arrest and accordingly represses cell division. Finally, Western blotting showed that NCPAG knockdown dysregulated cell cycle- and epithelial-mesenchymal transition-related molecules. CONCLUSION: Overall, the results reveal that NCAPG overexpression is a candidate prognostic biomarker and potential therapeutic target in GC.