Long non-coding RNA CRNDE is a novel tumor promoter by modulating PI3K/AKT signal pathways in human gastric cancer

D.-X. Du, D.-B. Lian, B.-H. Amin, W. Yan

Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China. ddcri377@yeah.net

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• Oncology

OBJECTIVE: Long non-coding RNA CRNDE (CRNDE) recently emerged as a carcinogenic promoter in various cancers including gastric cancer (GC). However, the functions and molecular mechanisms of CRNDE to GC are still largely unclear. The aim of this study was to investigate the clinical significance and functional mechanisms of CRNDE expression in GC.

PATIENTS AND METHODS: The expression of CRNDE was detected by quantitative Real-time PCR (qRT-PCR) in GC specimens and cell lines. The correlation between the CRNDE expression and clinicopathological parameters was investigated. Survival rate was determined with Kaplan-Meier and statistically analyzed with the log-rank method between groups. Subsequently, the significance of survival variables was analyzed using the Cox multivariate proportional hazards model. Then, MTT and Transwell assays were used to assess cell proliferation, migration and invasion capacity. Finally, Western blot analysis was performed to explore the effects of CRNDE knockdown on the PI3K/Akt pathway.

RESULTS: We observed that expression of CRNDE was higher in GC tissues and cells compared with the normal gastric tissue and normal gastric cell lines. High expression of CRNDE was correlated with invasion depth (p = 0.006), TNM stage (p = 0.010) and lymph node metastasis (p = 0.005). Furthermore, high CRNDE expression was associated with shorter overall survival (p = 0.0066) of GC patients. Multivariate analysis confirmed that high CRNDE expression was a significant independent predictor of poor survival in GC. In vitro assay indicated that knockdown of CRNDE inhibited cell proliferation, migration and invasion of GC. Finally, the data of Western blot showed that CRNDE exerted its oncogenic role by affecting PI3K/AKT signaling pathways.

CONCLUSIONS: Our findings indicate that CRNDE plays an important role in promoting GC progression and may represent a novel prognostic biomarker in GC.

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