miRNA-181a通过负调节肿瘤抑制基因KLF6促进胃癌增殖.pdfVIP

Tumor Biol. (2012) 33:1589– 1597 DOI 10.1007/s13277-012-0414-3 RESEARCH ARTICLE MicroRNA-181a promotes gastric cancer by negatively regulating tumor suppressor KLF6 Xiangyang Zhang Yuqiang Nie Yanlei Du Jie Cao Bo Shen Yuyuang Li Received: 7 March 2012 /Accepted: 30 April 2012 /Published online: 12 May 2012 # International Society of Oncology and BioMarkers (ISOBM) 2012 Abstract MicroRNAs have emerged as crucial regulators of women [ 1]. Despite recent advances in surgical technique, tumorigenesis. However, it remains unknown whether miR- diagnostic method and new chemotherapy regimens, no 181a is involved in the pathogenesis of gastric cancer. In this effective targeting therapy is available for gastric cancer, study, we found that miR-181a is overexpressed in human mainly due to a lack of complete understanding of the gastric cancer tissues. Ectopic expression of miR-181a mimic molecular mechanisms underlying gastric cancer develop- promoted the proliferation, colony formation, migration, and ment. Multiple studies indicate that gastric cancer is a poly- invasion and inhibited the apoptosis of SGC-7901 gastric genic disease that arises via the dysregulation of many cancer cells, whereas ectopic expression of miR-181a inhibi- related genes [2]. Many well-characterized tumor suppressor tor inhibited the malignant phenotypes of SGC-7901 cells. genes and oncogenes have been analyzed to better define Site-directed mutagenesis and luciferase reporter assay dem- their respective roles in gastric cancer development and onstrated that miR-181a repressed KLF6 expression by target- progression, but only a few consistent and frequent genetic ing its 3′-UTR. Western blot analysis further showed that alterations have been identified [3]. Germline mutations in KLF6 protein was significa