Facilitating colorectal cancer cell metastasis by targeted binding of long non-coding RNA ENSG00000231881 with miR-133b via VEGFC signaling pathway

Abstract

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.

Keywords: Colorectal cancer; ENSG00000231881; Long non-coding RNA; Metastasis; VEGFC; miR-133b.