长链非编码 RNA CRNDE 通过调节人胃癌中的 PI3K/AKT 信号通路成为一种新型肿瘤促进因子。
Long non-coding RNA CRNDE is a novel tumor promoter by modulating PI3K/AKT signal pathways in human gastric cancer.
机构信息
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China.
出版信息
Eur Rev Med Pharmacol Sci. 2017 Dec;21(23):5392-5398. doi: 10.26355/eurrev_201712_13925.
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.
目的
长链非编码 RNA CRNDE（CRNDE）最近在包括胃癌（GC）在内的各种癌症中被发现是一种致癌促进物。然而，CRNDE 对 GC 的功能和分子机制仍在很大程度上不清楚。本研究旨在探讨 CRNDE 表达在 GC 中的临床意义和功能机制。
方法
通过定量实时 PCR（qRT-PCR）检测 GC 标本和细胞系中 CRNDE 的表达。研究 CRNDE 表达与临床病理参数之间的相关性。通过 Kaplan-Meier 法和组间对数秩检验统计分析生存率。随后，使用 Cox 多变量比例风险模型分析生存变量的意义。然后，使用 MTT 和 Transwell 测定法评估细胞增殖、迁移和侵袭能力。最后，通过 Western blot 分析探讨 CRNDE 敲低对 PI3K/Akt 通路的影响。
结果
我们观察到，与正常胃组织和正常胃细胞系相比，GC 组织和细胞中 CRNDE 的表达更高。CRNDE 高表达与浸润深度（p = 0.006）、TNM 分期（p = 0.010）和淋巴结转移（p = 0.005）相关。此外，CRNDE 高表达与 GC 患者的总生存期较短相关（p = 0.0066）。多因素分析证实，CRNDE 高表达是 GC 患者不良生存的显著独立预测因子。体外试验表明，CRNDE 敲低抑制 GC 细胞的增殖、迁移和侵袭。最后，Western blot 数据表明，CRNDE 通过影响 PI3K/AKT 信号通路发挥其致癌作用。
结论
我们的研究结果表明，CRNDE 在促进 GC 进展中起重要作用，可能代表 GC 的一种新的预后生物标志物。
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