Please use this identifier to cite or link to this item:
Title: Loss of SNAIL regulated miR-128-2 on chromosome 3p22.3 targets multiple stem cell factors to promote transformation of mammary epithelial cells
Authors: Qian, P.
Banerjee, A.
Wu, Z.-S.
Zhang, X.
Wang, H.
Pandey, V.
Zhang, W.-J.
Lv, X.-F.
Tan, S.
Lobie, P.E. 
Zhu, T.
Issue Date: 15-Nov-2012
Source: Qian, P., Banerjee, A., Wu, Z.-S., Zhang, X., Wang, H., Pandey, V., Zhang, W.-J., Lv, X.-F., Tan, S., Lobie, P.E., Zhu, T. (2012-11-15). Loss of SNAIL regulated miR-128-2 on chromosome 3p22.3 targets multiple stem cell factors to promote transformation of mammary epithelial cells. Cancer Research 72 (22) : 6036-6050. ScholarBank@NUS Repository.
Abstract: A discontinuous pattern of LOH at chromosome 3p has been reported in 87% of primary breast cancers. Despite the identification of several tumor suppressor genes in this region, there has yet to be a detailed analysis of noncoding RNAs including miRNAs in this region. In this study, we identified 16 aberrant miRNAs in this region and determined several that are frequently lost or amplified in breast cancer. miR-128-2 was the most commonly deleted miRNA. Embedded in the intron of the ARPP21 gene at chromosome 3p22.3, miR-128-2 was frequently downregulated along with ARPP21 in breast cancer, where it was negatively associated with clinicopathologic characteristics and survival outcome. Forced expression of miR-128 impeded several oncogenic traits of mammary carcinoma cells, whereas depleting miR-128-2 expression was sufficient for oncogenic transformation and stem cell-like behaviors in immortalized nontumorigenic mammary epithelial cells, both in vitro and in vivo. miR-128-2 silencing enabled transforming capacity partly by derepressing a cohort of direct targets (BMI1, CSF1, KLF4, LIN28A, NANOG, and SNAIL), which together acted to stimulate the PI3K/AKT and STAT3 signaling pathways. We also found that miR-128-2 was directly downregulated by SNAIL and repressed by TGF-β signaling, adding 2 additional negative feedback loops to this network. In summary, we have identified a novel TGF-β/SNAIL/miR-128 axis that provides a new avenue to understand the basis for oncogenic transformation of mammary epithelial cells. ©2012 AACR.
Source Title: Cancer Research
ISSN: 00085472
DOI: 10.1158/0008-5472.CAN-12-1507
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Feb 27, 2018


checked on Feb 14, 2018

Page view(s)

checked on Mar 12, 2018

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.