High level of TXNDC9 predicts poor prognosis and contributes to the NF-κB-regulated metastatic potential in gastric cancer

Qun-Cao Yang, Nan Hao, Rui-Hua Li, Yuan-Yuan Duan,  Yong Zhang

Abstract:

Gastric cancer (GC) is the most frequent malignant tumor in the digestive system, with high metastasis potential and poor prognosis. This study aimed to investigate the prognostic value and biological function of thioredoxin domain-containing protein 9 (TXNDC9) in GC. The expression of TXNDC9 was analyzed based on The Cancer Genome Atlas (TCGA) database. The prognostic value of TXNDC9 was evaluated by Kaplan-Meier curves and Cox regression analysis. The mRNA and protein expression of TXNDC9 were analyzed using quantitative real-time PCR and western blot analysis. The effects of TXNDC9 on GC cell invasion and EMT were assessed in vitro, and its effects on tumorigenesis were confirmed using animal experiments. The activity of the NF-κB signaling pathway was examined by both in vitro and in vivo experiments. TXNDC9 was highly expressed in GC tissues and cell lines. A high level of TXNDC9 was associated with poor overall survival and served as an independent prognostic biomarker in GC patients. The knockdown of TXNDC9 led to restrained GC cell invasion, microtubule formation, and EMT in vitro, and suppressed tumorigenesis in vivo. In addition, the NF-κB signaling pathway was demonstrated to mediate the functional role of TXNDC9 in GC. In conclusion, this study found that high TXNDC9 predicted poor prognosis in GC, and served as an oncogene by enhancing tumor cell invasion and EMT through the NF-κB signaling pathway.