Significant association of DIRC1 overexpression with tumor progression and poor prognosis in gastric cancer

OBJECTIVE: DIRC1, Disrupted in Renal Cancer 1, was identified as a breakpoint-spanning gene in a chromosomal translocation, which was associated with the onset and progression of some cancers. However, the expression in human gastric cancer (GC) and the role of DIRC1 in human gastric tumorigenesis are unknown. Thereby, the main purpose of this study was to unearth the association of DIRC1 with GC. MATERIALS AND METHODS: By analyzing The Cancer Genome Atlas (TCGA) datasets, the expression of DIRC1 in GC and normal gastric tissues were compared. Besides, its association with clinicopathological significance, overall survival (OS) and independent prognosis were analyzed by Pearson's Chi-square(2) test, Kaplan-Meier method and Cox proportional hazards model, respectively. Functionally, the knockdown of DIRC1 was performed by siRNA method: moreover, its effects on the proliferation and metastasis of GC cells were examined by CCK-8 and transwell assays. Furthermore, the key markers of protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling were tested by Western blot assay. RESULTS: The results showed that high ex- pression of DIRC1 was found in GC tissues compared with normal gastric tissues. High expression of DIRC1 was associated with more cases of severer tumor malignancy and shorter OS: besides, high-level of DIRC1 was suggested to be an independent prognostic factor for GC. Furthermore, the knockdown of DIRC1 inhibited SGC-7901 GC cells proliferation, migration and invasion. Mechanically, the activity of AKT/mTOR signaling was suppressed by the knockdown of DIRC1. CONCLUSIONS: These findings offer clinical associations and an in vitro evidence showing that the knockdown of DIRC1 impeded the GC carcinogenicity possibly via suppression of AKT/mTOR signaling. This work might provide a potential therapeutic target for GC treatment.