文章：

微小RNA-532-3p通过抑制FOXM1调控结直肠癌细胞增殖与侵袭能力

MicroRNA-532-3p Modulates Colorectal Cancer Cell Proliferation and Invasion via Suppression of FOXM1

原文发布日期：2 September 2024

DOI: 10.3390/cancers16173061

类型: Article

开放获取: 是

英文摘要：

Colorectal cancer (CRC) is a heterogeneous disease and classified into various subtypes, among which transcriptional alterations result in CRC progression, metastasis, and drug resistance. Forkhead-box M1 (FOXM1) is a proliferation-associated transcription factor which is overexpressed in CRC and the mechanisms ofFOXM1regulation have been under investigation. Previously, we showed that FOXM1 binds to promoters of certain microRNAs. Database mining led to several microRNAs that might interact withFOXM13’UTR. The interactions between shortlisted microRNAs andFOXM13’UTR were quantitated by a dual-luciferase reporter assay. MicroRNA-532-3p interacted with the 3’UTR of theFOXM1mRNA transcript most efficiently. MicroRNA-532-3p was ectopically overexpressed in colorectal cancer (CRC) cell lines, leading to reduced transcript and protein levels ofFOXM1andcyclin B1, a direct transcriptional target of FOXM1. Further, a clonogenic assay was conducted in overexpressed miR-532-3p CRC cells that revealed a decline in the ability of cells to form colonies and a reduction in migratory and invading potential. These alterations were reinforced at molecular levels by the altered transcript and protein levels of the conventional EMT markers E-cadherin and vimentin. Overall, this study identifies the regulation ofFOXM1by microRNA-532-3p via its interaction withFOXM13’UTR, resulting in the suppression of proliferation, migration, and invasion, suggesting its role as a tumor suppressor in CRC.

摘要翻译： 

结直肠癌是一种异质性疾病，可分为多种亚型，其中转录水平改变导致其进展、转移及耐药。叉头框蛋白M1是一种增殖相关转录因子，在结直肠癌中过度表达，其调控机制尚在研究中。前期研究发现FOXM1可与特定微小RNA启动子结合。通过数据库挖掘，我们筛选出可能与FOXM1 3'UTR相互作用的多个微小RNA。经双荧光素酶报告基因检测定量分析，发现微小RNA-532-3p与FOXM1 mRNA转录本3'UTR的相互作用最为显著。在结直肠癌细胞系中外源性过表达微小RNA-532-3p，可降低FOXM1及其直接转录靶标细胞周期蛋白B1的转录水平和蛋白表达。进一步克隆形成实验显示，过表达miR-532-3p的结直肠癌细胞克隆形成能力下降，迁移和侵袭潜能减弱。分子水平检测发现，上皮间质转化标志物E-钙黏蛋白和波形蛋白的转录及蛋白表达发生改变，印证了上述表型变化。本研究首次阐明微小RNA-532-3p通过与FOXM1 3'UTR相互作用调控FOXM1表达，进而抑制结直肠癌细胞增殖、迁移和侵袭，提示其可能发挥肿瘤抑制因子作用。

原文链接：

MicroRNA-532-3p Modulates Colorectal Cancer Cell Proliferation and Invasion via Suppression of FOXM1