The Prognostic and Chemotherapeutic Value of miR-296 in Esophageal Squamous Cell Carcinoma
The Prognostic and Chemotherapeutic Value of miR-296 in Esophageal Squamous Cell Carcinoma
复制标题
miR-296在食管鳞状细胞癌中的预后和化疗价值。
DOI：
10.1097/sla.0b013e3181dd4ea9
复制
发表时间：
2010-06-01
影响因子：
9
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Hong, Liu;Han, Yu;Fan, Daiming
目的：我们的目的是首先研究miRNAs在食管鳞状细胞癌中的表达模式，然后将其与邻近的良性食管组织进行比较。背景资料：食管鳞状细胞癌在我国发病率较高，但其发病机制尚不清楚。方法：应用miRNA芯片、实时荧光定量PCR和北方印迹技术，对食管癌组织中miRNA的表达差异进行分析。结果：共鉴定出9个表达上调的miRNAs和3个表达下调的miRNAs。miR-296在食管炎组织、食管原位癌和食管鳞状细胞癌组织中的表达逐渐上调。miR-296的低表达能够通过预测生存期（中位数，23.7 vs. 12.9个月）区分淋巴结阳性疾病的长期生存者和20个月内死亡的患者。下调miR-296可能通过调控cyclin D1和p27在体内外抑制食管癌细胞的生长。下调miR-296可使食管癌细胞对P-糖蛋白相关和非相关药物敏感，并可能促进ADR诱导的细胞凋亡，同时增加ADR的蓄积和减少ADR的释放量。结论：miR-296可能在食管癌的发生发展中起重要作用，是食管癌治疗的潜在靶点。
Objective: We aimed first to investigate the expression pattern of miRNAs in esophageal squamous cell cancer and then compared it with those of adjacent benign esophageal tissues. The role of target miRNAs in the development of esophageal cancer was further detected.Summary Background Data: Although esophageal squamous cell carcinoma was of high incidence in China, the pathogenic mechanism remained largely unknown. A better understanding of changes in miRNA expression during esophageal carcinogenesis might lead to possible improvements in the diagnosis and treatment for esophageal carcinoma.Methods: The miRNAs were identified differentially expressed in esophageal cancer tissues, using miRNA microarray, real-time PCR, and Northern blot. The role of target miRNAs was investigated by in vitro and in vivo assay.Results: Nine miRNAs with increased expression and 3 with decreased expression were identified. The expression of miR-296 was found increasingly up-regulated in esophagitis tissues, esophageal carcinoma in situ, and esophageal squamous cell cancer tissues. Low expression of miR-296 was able to distinguish long-term survivors with node-positive disease from those dying within 20 months by predicting survival (median, 23.7 vs. 12.9 months). Downregulation of miR-296 might inhibit growth of esophageal cancer cells in vitro and in vivo through regulation of cyclin D1 and p27. Downregulation of miR-296 could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-nonrelated drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Downregulation of miR-296 could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of MDR1, but up-regulate the expression of Bax.Conclusions: MiR-296 might play important roles in the pathogenesis of esophageal cancer and considered as a potential target for this malignancy intervention.