通过 VEGFC 信号通路靶向结合长链非编码 RNA ENSG00000231881 与 miR-133b 促进结直肠癌细胞转移。
Facilitating colorectal cancer cell metastasis by targeted binding of long non-coding RNA ENSG00000231881 with miR-133b via VEGFC signaling pathway.
机构信息
Gastrointestinal Surgery Ward, Xiangya 3rd Hospital, Centre South University, Hunan, 410013, China.
Operation Center, Xiangya 3rd Hospital, Centre South University, Hunan, 410013, China.
出版信息
Biochem Biophys Res Commun. 2019 Jan 29;509(1):1-7. doi: 10.1016/j.bbrc.2018.08.004. Epub 2018 Dec 20.
BACKGROUND
Colorectal cancer mainly metastasizes through the lymphatic pathways and is associated with a high mortality rate. It is one of the leading causes of cancer-related deaths. In this study, the effects of long non-coding RNA (lncRNA) ENSG00000231881 on the metastasis of colorectal cancer cells were evaluated.
METHODS
The expression level of ENSG00000231881 in colorectal cancer tissues was detected with bioinformatics analysis and quantitative polymerase chain reaction (qPCR) assay. Functional colorectal cancer cell models for the overexpression and interference expression of ENSG00000231881 were established. MTT, transwell, tube formation, qPCR, and western blot assays were performed to detect changes in various cellular functions and expression levels of key factors (miR-133b and vascular endothelial growth factor C [VEGFC]) in ENSG00000231881 functional models. Dual luciferase assay was performed to verify the binding relationship between ENSG00000231881 and miR-133b.
RESULTS
ENSG00000231881 expression level was substantially higher in colorectal cancer tissues than in paracancerous tissues and correlated with malignancy and prognosis. In colorectal cancer cells, ENSG00000231881 overexpression significantly promoted cell proliferation, metastasis, and tube formation in lymphatic epithelium, decreased miR-133b expression, and increased VEGFC expression. On the contrary, ENSG00000231881 interference expression showed exactly opposite results. ENSG00000231881 could bind to miR-133b and consequently affect the cell functions through the regulation of VEGFC expression via miR-133b.
CONCLUSION
ENSG00000231881 binds to miR-133b via competitive endogenous RNA (ceRNA) mechanism and regulates the VEGFC signaling pathway, consequently leading to the metastasis of colorectal cancer cells. Our study provides a theoretical basis for the use of ENSG00000231881 as a therapeutic target for gene-targeted therapy in colorectal cancer.
背景
结直肠癌主要通过淋巴途径转移，死亡率高，是癌症相关死亡的主要原因之一。本研究评估了长链非编码 RNA（lncRNA）ENSG00000231881 对结直肠癌细胞转移的影响。
方法
通过生物信息学分析和定量聚合酶链反应（qPCR）检测结直肠癌组织中 ENSG00000231881 的表达水平。建立 ENSG00000231881 过表达和干扰表达的功能结直肠癌细胞模型。MTT、transwell、管形成、qPCR 和 Western blot 检测 ENSG00000231881 功能模型中各种细胞功能和关键因子（miR-133b 和血管内皮生长因子 C [VEGFC]）表达水平的变化。双荧光素酶报告实验验证 ENSG00000231881 与 miR-133b 的结合关系。
结果
ENSG00000231881 在结直肠癌组织中的表达水平明显高于癌旁组织，与恶性程度和预后相关。在结直肠癌细胞中，ENSG00000231881 过表达显著促进淋巴上皮细胞的增殖、转移和管形成，降低 miR-133b 的表达，增加 VEGFC 的表达。相反，ENSG00000231881 干扰表达则显示出完全相反的结果。ENSG00000231881 可以通过竞争性内源性 RNA（ceRNA）机制与 miR-133b 结合，通过 miR-133b 调节 VEGFC 信号通路，从而导致结直肠癌细胞的转移。
结论
ENSG00000231881 通过竞争性内源性 RNA（ceRNA）机制与 miR-133b 结合，并调节 VEGFC 信号通路，从而导致结直肠癌细胞的转移。本研究为将 ENSG00000231881 作为结直肠癌基因靶向治疗的治疗靶点提供了理论依据。
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