miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis (Nat Cell Biol, 2010, 12:247-256)

報告日期: 2010/10/08
報告時間: 16:00/16:50
報告學生: 盧佳杏
講評老師: 呂佩融
附件下載:

Full Text:  http://basicmed.med.ncku.edu.tw/admin/up_img/991008-3.pdf

miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis

Li Ma et al, Nature cell biology 12, 247-256, 2010

 

Speaker: 盧佳杏 

Commentator: 呂佩融 老師

Date: 10/08/2010

Time: 04:10 p.m.

Room: 602

 

Abstract

Cancer metastasis is the overwhelming cause of mortality in patients with solid tumours. Accumulating evidence indicates that epithelial-mesenchymal transition (EMT), a process in which cells undergo a switch from an epithelial phenotype to a mesenchymal phenotype, gives rise to the dissemination of single carcinoma cells from the sites of the primary. And a small-noncoding RNAs named microRNAs are associated with cancer progression and therapeutic outcome in several human cancers. Although the oncogenic or tumor-suppressing functions of several microRNAs have been characterized, the mechanistic roles played by microRNAs directly regulate the EMT is still unclear. In this study, the author found that miR-9, which is over-expressed in breast cancer, directly targets the E-cadherin. Loss of E-cadherin promotes cancer cell metastasis not induce EMT to form micro-metastases in vivo but contribute angiogenesis by activate β-catenin signaling. On the other hand, silencing miR-9 in highly metastatic cells using ‘miRNA sponge’ blocks metastasis. Furthermore, the upregulation of miR-9 is activated by MYC and MYCN that directly bind to miR9-3 locus. In human samples, miR-9 levels significantly correlate with MYCN amplification and metastatic status. In conclusion, the author defines the function of miR-9 and it can be regulated by oncoprotein. These findings illuminate another molecular mechanism for metastasis and microRNAs might as novel clinical biomarkers and therapeutic targets in cancer progression.

 

References

1. Thiery, J. P. Epithelial-mesenchymal transitions in tumour progression. Nature Rev. Cancer 2, 442-454 (2002).

2. Ma, L., Teruya-Feldstein, J. & Weinberg, R. A. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449, 682-688 (2007).

3. Ma, L. & Weinberg, R. A. Micromanagers of malignancy: role of microRNAs in regulating metastasis. Trends Genet. 24, 448-456 (2008).