Upregulation of circHIPK3 promotes the progression of gastric cancer via Wnt/β-catenin pathway and indicates a poor prognosis

W.-G. Liu, Q. Xu

Department of General Surgery, Beijing Bo’ai Hospital, China Rehabilitation Research Center, Beijing, China. tsingcrrc@sina.cn

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• Oncology

OBJECTIVE: To elucidate the regulatory effect of circular RNA HIPK3 (circHIPK3) on the progression of gastric cancer (GC) by regulating the Wnt/β-catenin pathway. We aim to reveal whether the abnormal expression of circHIPK3 could predict the poor prognosis of GC.
PATIENTS AND METHODS: CircHIPK3 level in GC tissues and paracancerous tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Its level in GC cell lines (BGC, MGC, SGC and MKN) and gastric mucosal cell line (GES) was examined as well. The correlation between the circHIPK3 level and overall survival of GC was analyzed by the Kaplan-Meier method. Regulatory effects of circHIPK3 on the proliferative ability of GC cells were evaluated by Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Migratory changes influenced by circHIPK3 were explored through wound healing assay. The expression levels of relative genes in the Wnt/β-catenin pathway were detected in GC cells with circHIPK3 knockdown. Finally, the Wnt/β-catenin pathway inhibitor PNU-74654 was applied for detecting its influence on cellular behaviors of GC cells.
RESULTS: CircHIPK3 level was higher in GC tissues relative to paracancerous tissues. Identically, its level was higher in GC cells compared with that of GES cells. The expression level of circHIPK3 was negatively correlated to the overall survival of GC patients. Silence of circHIPK3 weakened proliferative and migratory abilities of GC cells. In addition, circHIPK3 knockdown markedly downregulated levels of WNT1, TCF4 and β-catenin. Application of PNU-74654 weakened the abilities of GC cells to proliferate and migrate.
CONCLUSIONS: CircHIPK3 promotes GC cells to proliferate and migrate by regulating the Wnt/β-catenin pathway. Upregulation of circHIPK3 indicates poor prognosis of GC patients.

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