Development of Novel Therapy by miRNA Targeting for Gastroenterological Cancer

在20个配对样本中，18个癌组织与匹配的正常上皮相比过表达miR-21。尤其是有淋巴结转移或静脉侵犯的患者，miR-21表达明显增高。所有7种ESCC细胞系也过表达miR-21，并且抗miR-21转染的ESCC细胞显示细胞增殖和侵袭显著降低。ESCC细胞中PDCD4蛋白表达与miR-21表达呈显著负相关。抗miR-21转染的ESCC细胞增加了PDCD4蛋白，而没有PDCD4-mRNA的差异，并增加了含有PDCD4 - 3'-UTR区域的内切酶报告基因活性。120例食管鳞癌中PDCD4蛋白表达阳性者生存期较阴性者延长。我们的研究结果表明，miR-21在ESCC的进展中起着关键作用，它可能成为一个新的治疗靶点。

Among 20 paired samples, 18 cancer tissues overexpressed miR-21 compared with matched normal epitheliums. Especially, patients with lymph node metastasis or venous invasion showed high expression of miR-21 significantly. All 7 ESCC cell lines also overexpressed miR-21 and anti-miR-21 transfected ESCC cells showed significant reduction in cellular proliferation and invasion. The PDCD4 protein in ESCC cells have inverse correlation with miR-21 expression significantly. Anti-miR-21 transfected ESCC cells increased PDCD4 protein without differences of PDCD4-mRNA and increased a luciferase-reporter activity containing the PDCD4-3'-UTR region. Among 120 ESCC samples, immunohistchmeistry study revealed that patients expressed PDCD4 protein prolonged survival compared with negative. Our results suggest miR-21 plays a pivotal role in progression of ESCC, and it might serve as a novel therapeutic target.