Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation (Mol Cell, 2009, 35:856-867)

報告日期: 2010/03/12
報告時間: 15:10/16:00
報告學生: 簡郡緯
講評老師: 陳炳焜
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990312-1.pdf

Hypoxia-inducible mir-210 regulates normoxic gene gxpression involved in tumor initiation

 

Commentator: Dr. Ben Kuen Chen (陳炳焜老師)

Speaker: Chen Wei Chien(簡郡緯)

Date: 2010.03.12

 

Abstract

Hypoxia regulates lots of genes expression through hypoxia inducible factor (HIF). The hypoxia-regulated genes, such as VEGF, GLUT-1 and mircoRNA, play important roles in tumor biology. However, how hypoxia regulates miRNA is still unclear. Herein, the author showed that mir-210 is regulated hypoxia through the binding of HIF-1 on the hypoxia-responsive element of mir-210. By argonaute immunopreciptating, 50 candidated genes were found as potential mir-210 targets and some of these genes were further validated by promoter assay. In functional assay, forced expression of mir-210 inhibited the initiation of tumor growth and the tumor size was negative correlated with mir-210 expression. Moreover, overexpression of mir-210-regulated gene reversed the inhibition of tumor growth by mir-21. Therefore, it suggested mir-210 may function as a tumor suppressor. In conclusion, these data provide the evidence of mir-210 which is regulated by hypoxia in the transcriptional level, and the importance of mir-210 in tumorigenesis. A better understanding of miRNAs in tumorigenesis will open new sight for therapeutic opportunities.

 

Reference

1.    mir-210: a sensor for hypoxic stress during tumorigenesis. Molecular Cell, 2009, 35: 737-738

2.   Hypoxia, gene expression, and metastasis. Cancer Metastasis Rev, 2007, 26:333-339