MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression (Plos One, 2008, 3(6):e2420, 1-14)

報告日期: 2008/11/18
報告時間: 15:10/16:00
報告學生: 翁菁憶
講評老師: 吳梨華
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971118-1.pdf

MicroRNA miR-328 Regulates Zonation Morphogenesis

by Targeting CD44 Expression

 

PLoS ONE  2008 Vol.3 p.2420

 

Speaker:  翁菁憶

Commentator:  吳梨華 老師

Time : 2008/11/18 15:10-14:00

place : 602 room

 

Abstract

Morphogenesis is crucial to initiate physiological development and tumor invasion. Authors show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. They have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this technique, they have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and capillary structure formation. Proteomic analysis indicated that miR-328 repressed CD44 expression. Luciferase activity assay indicated that harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immunohistochemistry stain also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion. Authors research paves the way to understand the roles of microRNAs in an unexplored area of development.

 

Reference

1.    Gumbiner BM. Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol. 2005;6(8):622-34.

2.   John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human MicroRNA targets. PLoS Biol. 2004 Nov;2(11):e363.