High expression of TCF12 contributes to gastric cancer development via being target regulated by miR-183 and activating PI3K/AKT pathway

Abstract

This study aimed to explore the role of transcription factor 12 (TCF12) in the process of gastric cancer (GC) and to elucidate its possible regulatory mechanism. The expression data of GC tissues and matched normal tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Survival analysis for GC patients with different levels of TCF12 was performed by the Kaplan-Meier analysis. In addition, TCF12 was suppressed in human GC cell lines AGS and MKN-45, followed by detecting cell biological processes (proliferation, apoptosis, migration, and invasion). Moreover, the association between TCF12 and the phosphatidylinositol 3-kinase (PI3K)/AKT signal was elucidated. Besides, the potential micro RNAs that could target TCF12 expression were explored. The results showed that TCF12 was highly expressed in GC tissues and TCF12 upregulation was associated with poor prognosis of GC patients. In addition, suppression of TCF12 significantly inhibited the proliferation, migration, and invasion of both AGS and MKN45 cells, as well as induced apoptosis of the two cell lines. Moreover, suppression of TCF12 significantly decreased the expression of p-AKT, cyclin D1, p-P70, and β-catenin in both AGS and MKN45 cells. Besides, TCF12 was target regulated by miR-183 in GC cells. Our findings reveal that TCF12 is upregulated in GC and its upregulation is associated with poor prognosis of GC patients. To sum up, downregulation of TCF12 may inhibit GC development via being target regulated by miR-183 and inhibiting the PI3K/AKT signal. TCF12 may function as a potential therapeutic target for GC.