环状 RNA hsa_circ_0010882 通过调控 PI3K/Akt/mTOR 信号通路促进胃癌的进展。
Circular RNA hsa_circ_0010882 promotes the progression of gastric cancer via regulation of the PI3K/Akt/mTOR signaling pathway.
机构信息
Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Feb;24(3):1142-1151. doi: 10.26355/eurrev_202002_20165.
OBJECTIVE
Accumulating studies have reported that circular RNAs (circRNAs) can act as novel prognostic biomarkers in multiple malignant tumors. Here, we conducted a study to investigate the potential function and molecular mechanism of action of hsa_circ_0010882 in gastric cancer (GC).
PATIENTS AND METHODS
The expression of hsa_circ_0010882 in the plasma of GC patients and in GC cell lines was verified by qRT-PCR. Its association with overall survival of GC patients was then analyzed by statistical analysis. Gain-of-function and loss-of-function assays were used to investigate the physiological function of hsa_circ_0010882 in GC cells in vitro in the context of proliferation, apoptosis, migration, and invasion. Moreover, the molecular mechanism of action of hsa_circ_0010882 was predicted using online databases and a literature review. A Western blot assay was used to detect the levels of proteins in the PI3K/Akt/mTOR signaling pathway.
RESULTS
We found that hsa_circ_0010882 expression was significantly upregulated in the plasma of GC patients and GC cell lines. Increased expression of hsa_circ_0010882 was significantly correlated with tumor size and histological grade. In addition, GC patients with higher expression of hsa_circ_0010882 had significantly lower overall survival than patients with lower expression of hsa_circ_0010882. Multivariate analysis showed that hsa_circ_0010882 expression could be an independent prognostic factor for overall survival. The proliferation, migration, and invasiveness of GC cell lines were inhibited following hsa_circ_0010882 knock-down, while GC cellular apoptosis increased. Further, overexpression of hsa_circ_0010882 leads to increased proliferation, migration, and invasiveness of GC cell lines. While apoptosis was higher in the GC cell line group with low expressing hsa_circ_0010882 than the control group, no significant difference in apoptosis was detected between the hsa_circ_0010882 overexpressing and the control group. Finally, a mechanistic analysis demonstrated that the hsa_circ_0010882 was positively associated with PI3K/Akt/mTOR signaling pathway.
CONCLUSIONS
Hsa_circ_0010882, as an oncogenic molecule, is highly expressed in the plasma of patients with GC and is associated with poor prognosis. It plays an important role in proliferation, migration, and invasive genotypes of GC cell lines via regulation of the PI3K/Akt/mTOR signaling pathway. Additionally, it might be a potential prognostic biomarker for GC patients.
目的
越来越多的研究表明，环状 RNA（circRNA）可以作为多种恶性肿瘤的新型预后生物标志物。在这里，我们进行了一项研究，以探讨 hsa_circ_0010882 在胃癌（GC）中的潜在功能和作用机制。
患者和方法
通过 qRT-PCR 验证了 GC 患者血浆和 GC 细胞系中 hsa_circ_0010882 的表达。然后通过统计分析分析 hsa_circ_0010882 与 GC 患者总生存期的相关性。体外通过增殖、凋亡、迁移和侵袭实验，利用 gain-of-function 和 loss-of-function 检测 hsa_circ_0010882 在 GC 细胞中的生理功能。此外，还通过在线数据库和文献综述预测 hsa_circ_0010882 的作用机制。通过 Western blot 检测 PI3K/Akt/mTOR 信号通路中蛋白的水平。
结果
我们发现 hsa_circ_0010882 在 GC 患者的血浆和 GC 细胞系中表达明显上调。hsa_circ_0010882 的高表达与肿瘤大小和组织学分级显著相关。此外，hsa_circ_0010882 表达较高的 GC 患者总生存期明显低于 hsa_circ_0010882 表达较低的患者。多因素分析表明，hsa_circ_0010882 表达可作为总生存期的独立预后因素。hsa_circ_0010882 敲低后 GC 细胞系的增殖、迁移和侵袭能力受到抑制，而 GC 细胞系的凋亡增加。此外，hsa_circ_0010882 的过表达导致 GC 细胞系的增殖、迁移和侵袭能力增加。hsa_circ_0010882 低表达组 GC 细胞系的凋亡高于对照组，但 hsa_circ_0010882 过表达组与对照组之间的凋亡无显著差异。最后，机制分析表明，hsa_circ_0010882 与 PI3K/Akt/mTOR 信号通路呈正相关。
结论
hsa_circ_0010882 作为一种致癌分子，在 GC 患者的血浆中高表达，并与不良预后相关。它通过调节 PI3K/Akt/mTOR 信号通路在 GC 细胞系的增殖、迁移和侵袭基因型中发挥重要作用。此外，它可能是 GC 患者的一个潜在预后生物标志物。
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