miR-9-5p 通过靶向 FOXP2 抑制细胞转移和上皮-间充质转化，并预测结直肠癌的预后。
MiR-9-5p suppresses cell metastasis and epithelial-mesenchymal transition through targeting FOXP2 and predicts prognosis of colorectal carcinoma.
机构信息
Department of Gastroenterology Surgery, Liaocheng People's Hospital, Liaocheng, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Aug;23(15):6467-6477. doi: 10.26355/eurrev_201908_18530.
OBJECTIVE
Colorectal carcinoma (CRC) is a common malignant tumor of the digestive tract that occurs in the colon, and the incidence is the third in the gastrointestinal tumor. Recently, the dysregulated expression of microRNA-9 (miR-9) has been identified in many human cancers. However, the special function of miR-9 in the progression of colorectal carcinoma (CRC) remains unknown.
PATIENTS AND METHODS
Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of miR-9-5p in 72 pairs of CRC tissues and cell lines. The correlation between miR-9-5p expression and clinical features or prognosis of CRC patients was analyzed. In addition, we examined the mRNA and protein expression levels of forkhead box P2 (FOXP2) using Western blot analysis and qRT-PCR. The functions of miR-9-5p and FOXP2 were investigated using transwell assay and epithelial-mesenchymal transition (EMT). The relation between miR-9-5p and FOXP2 was confirmed by the dual-luciferase assay.
RESULTS
In this study, down-regulation of miR-9-5p and up-regulation of the forkhead box P2 (FOXP2) were detected in CRC tissues and cell lines. Moreover, miR-9-5p was found to inhibit cell metastasis and EMT in CRC. In addition, it was confirmed that miR-9-5p directly targeted FOXP2 in CRC. Furthermore, FOXP2 had a carcinogenic effect on CRC. And the overexpression of FOXP2 weakened the suppressive effect of miR-9-5p in CRC. Of note, we observed found that the low expression of miR-9-5p and the high expression of FOXP2 were correlated with poor prognosis of CRC patients.
CONCLUSIONS
MiR-9-5p suppressed cell metastasis and EMT through targeting FOXP2. Furthermore, dysregulation of miR-9-5p predicted the prognosis of CRC patients. Therefore, miR-9-5p may be a biomarker for cell metastasis and a prognostic factor for CRC patients. MiR-9-5p/FOXP2 axis will provide a new breakthrough in the diagnosis and treatment of CRC.
目的
结直肠癌（CRC）是一种常见的消化道恶性肿瘤，发生在结肠，其发病率在胃肠道肿瘤中排名第三。最近，miR-9 的表达失调已在许多人类癌症中被发现。然而，miR-9 在结直肠癌（CRC）进展中的特殊功能仍然未知。
患者和方法
采用实时定量聚合酶链反应（qRT-PCR）检测 72 对 CRC 组织和细胞系中 miR-9-5p 的表达。分析 miR-9-5p 表达与 CRC 患者临床特征和预后的相关性。此外，我们使用 Western blot 分析和 qRT-PCR 检测叉头框 P2（FOXP2）的 mRNA 和蛋白表达水平。通过 Transwell 检测和上皮间质转化（EMT）研究 miR-9-5p 和 FOXP2 的功能。通过双荧光素酶报告基因实验证实 miR-9-5p 和 FOXP2 之间的关系。
结果
本研究发现，CRC 组织和细胞系中 miR-9-5p 下调，FOXP2 上调。此外，miR-9-5p 可抑制 CRC 细胞转移和 EMT。此外，证实 miR-9-5p 可在 CRC 中直接靶向 FOXP2。此外，FOXP2 对 CRC 具有致癌作用。并且 FOXP2 的过表达削弱了 miR-9-5p 在 CRC 中的抑制作用。值得注意的是，我们观察到 miR-9-5p 低表达和 FOXP2 高表达与 CRC 患者预后不良相关。
结论
miR-9-5p 通过靶向 FOXP2 抑制细胞转移和 EMT。此外，miR-9-5p 的失调可预测 CRC 患者的预后。因此，miR-9-5p 可能是细胞转移的生物标志物和 CRC 患者的预后因素。miR-9-5p/FOXP2 轴将为 CRC 的诊断和治疗提供新的突破。
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