E2F1-regulated microRNAs impair TGFb-dependent cell-cycle arrest and apoptosis in gastric cancer (Cancer Cell, 2008, 13:272-286)

報告日期: 2008/11/14
報告時間: 15:10/16:00
報告學生: 郭怡孜
講評老師: 陳玉玲
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971114-1.pdf

E2F1-Regulated MicroRNAs Impair TGFb-Dependent Cell-Cycle Arrest and Apoptosis in Gastric Cancer

 

Fabio Petrocca, Rosa Visone, Mariadele Rapazzotti Onelli, Manisha H. Shah, Milena S. Nicoloso,Ivana de Martino, Dimitrios Iliopoulos, Emanuela Pilozzi, Chang-Gong Liu, Massimo Negrini, Luigi Cavazzini, Stefano Volinia, Hansjuerg Alder, Luigi P. Ruco, Gustavo Baldassarre, Carlo M. Croce, and Andrea Vecchione

 

Cancer Cell 13, 272–286, March 2008

 

Speaker : Yi-Zih Kuo (郭怡孜)

Commentator : 陳玉玲

Date : 2008/11/14 15:00-16:00

Room : 602

 

Abstract

Upregulation of E2F1 activity and resistance to TGFb are hallmarks of gastric cancer. MicroRNAs (miRNAs) are small non-coding RNAs in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Although recent studies suggest that miRNAs can function as tumor suppressors or oncogenes in human carcinogenesis. In this study, the authors to explore the possibility that miRNAs may be involved in gastric tumorigenesis. They identified miR-106b-25 cluster overexpression in gastric cancer by a custom miRNA microarray and also found that miR-106b-25 transcription in gastric tumors is driven by it host gene, Mcm7. E2F1 is a transcription factor that transactivates a variety of genes involved in chromosomal DNA replication, including mcm7, so they show that miR-106b-25 cluster is activated by E2F1 and negatively control E2F1. Next, they used in silico assay to find p21 and Bim, the two downstream effectors of TGFb-dependent cell cycle arrest and apoptosis as miR-106b-25 target gene. Moreover, the results display that miRNAs impairs the TGFb tumor suppressor pathway, interfering with the expression of p21 and Bim. These findings indicate that E2F1 posttranscriptional regulation and may play a key role in the development of TGFb resistance in gastric cancer.

 

Reference

1.  Suzuki, T., Yasui, W., Yokozaki, H., Naka, K., Ishikawa, T., and Tahara, E. (1999). Expression of the E2F family in human gastrointestinal carcinomas. Int. J. Cancer 81, 535–538.

2.  Park, K., Kim, S.J., Bang, Y.J., Park, J.G., Kim, N.K., Roberts, A.B., and Sporn,M.B. (1994). Genetic changes in the transforming growth factor beta (TGFbeta) type II receptor gene in human gastric cancer cells: Correlation with sensitivity to growth inhibition by TGF-beta. Proc. Natl. Acad. Sci. USA 91, 8772–8776.