LncRNA CTC-497E21.4 通过调节 miR-22/NET1 轴通过 RhoA 信号通路促进胃癌的进展。
LncRNA CTC-497E21.4 promotes the progression of gastric cancer via modulating miR-22/NET1 axis through RhoA signaling pathway.
机构信息
Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China.
School of Public Health, Nantong University, Nantong, China.
出版信息
Gastric Cancer. 2020 Mar;23(2):228-240. doi: 10.1007/s10120-019-00998-w. Epub 2019 Aug 26.
BACKGROUND
Long non-coding RNAs (lncRNAs) have emerged as important roles in gastric cancer (GC). However, the role of the dysregulated lncRNAs in GC remained large unknown. We investigated the clinical significance, biological function and mechanism of CTC-497E21.4 in GC.
METHODS
Firstly, RTFQ-PCR was used to detect the expression of CTC-497E21.4 in GC. Furthermore, knockdown of CTC-497E21.4 was conducted to assess the effect of CTC-497E21.4 in vitro and vivo. Subcellular localization of CTC-497E21.4 was determined by nuclear plasmolysis PCR and FISH. We also predicted CTC-497E21.4 binding miRNAs and downstream target genes and evaluated its regulation of miR-22 by acting as a ceRNA.
RESULT
CTC-497E21.4 was upregulated in GC tissues and GC cell lines (P < 0.05), and the expression was associated with depth of invasion, lymph node metastasis, and neurological invasion. Besides, knockdown of CTC-497E21.4 inhibited cell proliferation, invasion and promoted cell cycle arrest in vitro and inhibited tumorigenesis in vivo. Mechanistic investigations indicated that CTC-497E21.4 acted as a ceRNA for miR-22 and regulated NET1 expression. CTC-497E21.4/miR-22-3p/NET1 participated in the RhoA signaling pathway in the GC progression.
CONCLUSION
CTC-497E21.4 competed with miR-22 to regulate the expression of NET1 and regulated the malignant progression of GC through RhoA signaling pathway.
背景
长链非编码 RNA（lncRNAs）在胃癌（GC）中发挥着重要作用。然而，失调的 lncRNAs 在 GC 中的作用仍知之甚少。我们研究了 CTC-497E21.4 在 GC 中的临床意义、生物学功能和机制。
方法
首先，使用 RTFQ-PCR 检测 GC 中 CTC-497E21.4 的表达。此外，通过敲低 CTC-497E21.4 来评估 CTC-497E21.4 在体外和体内的作用。通过核质分离 PCR 和 FISH 确定 CTC-497E21.4 的亚细胞定位。我们还预测了 CTC-497E21.4 结合的 miRNAs 和下游靶基因，并评估了其作为 ceRNA 对 miR-22 的调节作用。
结果
CTC-497E21.4 在 GC 组织和 GC 细胞系中上调（P<0.05），其表达与浸润深度、淋巴结转移和神经侵犯有关。此外，敲低 CTC-497E21.4 可抑制细胞增殖、侵袭，促进细胞周期停滞，在体内抑制肿瘤发生。机制研究表明，CTC-497E21.4 作为 miR-22 的 ceRNA 并调节 NET1 表达。CTC-497E21.4/miR-22-3p/NET1 参与 GC 进展中的 RhoA 信号通路。
结论
CTC-497E21.4 与 miR-22 竞争调节 NET1 的表达，并通过 RhoA 信号通路调节 GC 的恶性进展。
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