Department of Traditional Chinese Medicine, Shanxi Cancer Hospital, Taiyuan, China.
Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):1778-1785. doi: 10.26355/eurrev_202002_20355.
The aim of this study was to explore the role of microRNA-802 (miRNA-802) in the progression of colorectal cancer (CRC) and the underlying mechanism.
The relative expression levels of miRNA-802 and FOXE1 in 40 paired CRC tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between miRNA-802 expression and the pathological indexes of CRC patients was assessed. Meanwhile, the prognostic potentials of miRNA-802 and FOXE1 in CRC patients were identified through the Kaplan-Meier method. After overexpression of miRNA-802, the changes in the proliferative, migratory, and invasive capacities of HT29 and HCT-8 cells were evaluated in vitro. The Dual-Luciferase Reporter Gene Assay was applied to investigate the binding relationship between miRNA-802 and FOXE1. Finally, the rescue experiments were carried out to uncover the role of the miRNA-802/FOXE1 axis in regulating the cellular behaviors of CRC.
MiRNA-802 was significantly downregulated in CRC tissues and cell lines. CRC patients with a low level of miRNA-802 had significantly higher rates of lymphatic metastasis and distant metastasis, as well as worse overall survival. The transfection of miRNA-802 mimics remarkably attenuated the proliferation, migration, and invasion of HT29 and HCT-8 cells. FOXE1 expression was significantly upregulated in CRC tissues and cell lines. Meanwhile, the expression of FOXE1 was negatively correlated with miRNA-802 in CRC tissues. A higher level of FOXE1 indicated the worse prognosis of CRC patients. The Dual-Luciferase Reporter Gene Assay further verified the binding relationship between FOXE1 and miRNA-802. Importantly, the overexpression of FOXE1 could reverse the regulatory effects of miRNA-802 on the cellular behaviors of CRC.
MiRNA-802 is significantly downregulated in CRC, and is closely related to lymphatic and distant metastasis of CRC. Furthermore, miRNA-802 alleviates the malignant progression of CRC via negatively regulating FOXE1.
本研究旨在探讨微小 RNA-802（miRNA-802）在结直肠癌（CRC）进展中的作用及其潜在机制。
采用实时定量聚合酶链反应（qRT-PCR）检测 40 对 CRC 组织及其相邻正常组织中 miRNA-802 和 FOXE1 的相对表达水平。评估 miRNA-802 表达与 CRC 患者病理指标的相关性。同时，采用 Kaplan-Meier 法确定 miRNA-802 和 FOXE1 对 CRC 患者的预后价值。过表达 miRNA-802 后，体外评估 HT29 和 HCT-8 细胞增殖、迁移和侵袭能力的变化。应用双荧光素酶报告基因检测 miRNA-802 与 FOXE1 的结合关系。最后，进行挽救实验以揭示 miRNA-802/FOXE1 轴在调节 CRC 细胞行为中的作用。
miRNA-802 在 CRC 组织和细胞系中表达明显下调。miRNA-802 低表达的 CRC 患者具有更高的淋巴转移和远处转移率，以及更差的总生存期。miRNA-802 模拟物的转染显著抑制 HT29 和 HCT-8 细胞的增殖、迁移和侵袭。FOXE1 在 CRC 组织和细胞系中表达明显上调。同时，CRC 组织中 FOXE1 的表达与 miRNA-802 呈负相关。FOXE1 水平较高提示 CRC 患者预后较差。双荧光素酶报告基因检测进一步验证了 FOXE1 与 miRNA-802 之间的结合关系。重要的是，FOXE1 的过表达可以逆转 miRNA-802 对 CRC 细胞行为的调节作用。
miRNA-802 在 CRC 中明显下调，与 CRC 的淋巴和远处转移密切相关。此外，miRNA-802 通过负向调节 FOXE1 减轻 CRC 的恶性进展。
