General Surgery, The Fifth People's Hospital of Jinan, Jinan, Shandong, China.
Department of Gastrointestinal Surgery, Jining First People's Hosptial, Jining, Shandong, China.
J Gene Med. 2020 Jul;22(7):e3183. doi: 10.1002/jgm.3183. Epub 2020 Mar 18.
MiR-1249 was demonstrated to be dysregulated and related to prognosis in cancers. It has been reported to be significantly down-regulated in colon adenocarcinoma (COAD). The present study aimed to explore the clinical value and biological roles of miR-1249 in the progression of COAD.
miRWalk was applied to predict potential targets of miR-1249. We investigated the expression patterns of miR-1249 and its potential target Four-Jointed Box Kinase 1 (FJX1) in COAD samples from The Cancer Genome Atlas (TCGA) or ONCOMINE database. Kaplan-Meier with a log-rank test was used to reveal the relationship between overall survival (OS) and miR-1249/FJX1. The predictive ability of miR-1249/FJX1 was investigated using univariate and multivariate Cox regression models. CCK-8 and Transwell assays were performed to determine whether miR-1249 was connected with cell viability, migration and invasion. A luciferase reporter assay was applied to verify the association of miR-1249 and FJX1 as its predicted target gene.
We predicted and confirmed FJX1 to be a target gene of miR-1249. MiR-1249 was down-regulated in COAD samples and cell lines. Univariate and multivariate analysis showed that the expression of FJX1 could be regarded as independent predictor for COAD. Moreover, miR-1249 and FJX1 were respectively the indicators of favorable and poor OS. MiR-1249 over-expression repressed cell growth, migration and invasion. Overexpression of FJX1 in cells treated with miR-1249 mimic abolished the inhibitory effect of miR-1249 on cell growth, migration and invasion.
miR-1249 exerts a suppressive effect on cell proliferation, migration and invasion in COAD, which is possibly achieved via modulating FJX1.
miR-1249 在癌症中表现为失调，并与预后相关。已有研究报道 miR-1249 在结肠腺癌（COAD）中显著下调。本研究旨在探讨 miR-1249 在 COAD 进展中的临床价值和生物学作用。
应用 miRWalk 预测 miR-1249 的潜在靶标。我们调查了 COAD 样本中 miR-1249 及其潜在靶标 Four-Jointed Box Kinase 1（FJX1）的表达模式，这些样本来自 The Cancer Genome Atlas（TCGA）或 ONCOMINE 数据库。Kaplan-Meier 对数秩检验用于揭示总生存期（OS）与 miR-1249/FJX1 之间的关系。单因素和多因素 Cox 回归模型用于研究 miR-1249/FJX1 的预测能力。CCK-8 和 Transwell 测定用于确定 miR-1249 是否与细胞活力、迁移和侵袭有关。荧光素酶报告基因测定用于验证 miR-1249 与 FJX1 作为其预测靶基因的关联。
我们预测并证实 FJX1 是 miR-1249 的靶基因。miR-1249 在 COAD 样本和细胞系中下调。单因素和多因素分析表明，FJX1 的表达可视为 COAD 的独立预测因子。此外，miR-1249 和 FJX1 分别是 COAD 患者良好和不良 OS 的指标。miR-1249 过表达抑制细胞生长、迁移和侵袭。在 miR-1249 模拟物处理的细胞中转染 FJX1 过表达质粒可消除 miR-1249 对细胞生长、迁移和侵袭的抑制作用。
miR-1249 在 COAD 中对细胞增殖、迁移和侵袭具有抑制作用，可能是通过调节 FJX1 实现的。
