Institute of Oncology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
Department of Gastroenterology, Changzhou Jintan People's Hospital, Changzhou, Jiangsu 213200, P.R. China.
Oncol Rep. 2017 Nov;38(5):3030-3038. doi: 10.3892/or.2017.5995. Epub 2017 Sep 25.
Increasing evidence suggests that miR-25 can function as an oncogene in different types of human malignancies, whereas little is known concerning the role of miR-25 in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the role of miR-25 in ESCC and to determine the molecular mechanisms underlying its function. The expression level of miR-25 was detected in primary ESCC tissues and cell lines by real-time quantitative PCR. We also assessed whether knockdown of miR-25 influences in vitro cell invasion and migration. Western blot analysis was used to detect the influence of miR-25 on a target gene, and Pearson analysis was used to calculate the correlation between the expression of a target gene and miR-25 in ESCC tissues. The results revealed that the relative level of miR-25 expression was significantly upregulated in ESCC tissues and cell lines. Expression of miR-25 in ESCC tissues was positively associated with depth of tumor invasion and tumor stage. Moreover, high miR-25 expression conferred poorer overall survival (OS), and a multivariate analysis revealed that miR-25 was an independent risk factor for OS. In addition, knockdown of miR-25 in ESCC cells significantly suppressed cell migration and invasion. Furthermore, we identified F-box and WD repeat domain-containing 7 (FBXW7) protein as a direct functional target of miR-25 in ESCC. In conclusion, the present study supports the potential of miR-25 as a prognostic predictor with its high expression in cancer tissues and its association with tumor progression by targeting FBXW7 in ESCC.
越来越多的证据表明，miR-25 在不同类型的人类恶性肿瘤中可以作为癌基因发挥作用，而关于 miR-25 在食管鳞状细胞癌（ESCC）中的作用知之甚少。本研究旨在探讨 miR-25 在 ESCC 中的作用，并确定其功能的分子机制。通过实时定量 PCR 检测 miR-25 在原发性 ESCC 组织和细胞系中的表达水平。我们还评估了 miR-25 下调是否会影响体外细胞侵袭和迁移。Western blot 分析用于检测 miR-25 对靶基因的影响，Pearson 分析用于计算 ESCC 组织中靶基因表达与 miR-25 之间的相关性。结果表明，miR-25 的表达水平在 ESCC 组织和细胞系中显著上调。ESCC 组织中 miR-25 的表达与肿瘤浸润深度和肿瘤分期呈正相关。此外，miR-25 高表达预示着总生存期（OS）较差，多变量分析显示 miR-25 是 OS 的独立危险因素。此外，ESCC 细胞中 miR-25 的下调显著抑制了细胞迁移和侵袭。此外，我们确定 F-box 和 WD 重复结构域包含蛋白 7（FBXW7）蛋白是 miR-25 在 ESCC 中的直接功能靶标。总之，本研究支持 miR-25 作为一种预后预测因子的潜力，其在癌症组织中的高表达及其通过靶向 FBXW7 在 ESCC 中与肿瘤进展的关联。
