Circular RNA circTNIK promotes tumor progression and metastasis in gastric cancer by regulating ZEB2.

Abstract

Tumor progression and distant metastasis are the main causes of deaths in gastric cancer. Growing evidence revealed that circular RNAs (circRNAs) play critical role in the pathology of malignant disease, the role of circRNAs in gastric cancer progression and metastasis is still unknown. Differentially expressed circRNAs was identified by circRNA microarray and validated by quantitative reverse transcription polymerase reaction. The biological function of circTNIK was evaluated by in vitro and in vivo experiments after ectopic expression or siRNA mediated knockdown of circTNIK. The interaction between circTNIK and miR-138-5p was determined by luciferase activity assay, RNA immunoprecipitation, and fluorescence in situ hybridization assays. circTNIK rather than linear TINK mRNA was significantly upregulated in gastric cancer tissues, cell lines compared with normal controls. Higher circTNIK expression was correlated with aggressive tumor phenotypes and poor overall survival in gastric cancer patients. Ectopic circTNIK expression promoted cell proliferation, invasion, tumorigenesis, and metastasis in gastric cancer cells whereas knockdown of circTNIK inhibited cell proliferation, invasion, tumorigenesis, and metastasis in gastric cancer cells. Importantly, circTNIK functions as a molecular sponge for miR-138-5p to regulate the expression of ZEB2. Overall, our study demonstrates how circTNIK regulates gastric cancer progression and metastasis by sponging miR-138-5p to modulate the expression of ZEB2. CircTNIK might be used as a prognostic biomarker in gastric cancer patients.