Abstract:
:Compared with the luminal subtype, the basal-like subtype of breast cancer has an aggressive clinical behavior, but the reasons for this difference between the two subtypes are poorly understood. We identified microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) as basal-like subtype-specific miRNAs that decrease expression of epithelial-specific genes and increase expression of mesenchymal-specific genes. In addition, expression of these miRNAs increased cell migration and invasion, which collectively are characteristics of the epithelial-to-mesenchymal transition (EMT). The basal-like transcription factor FOSL1 (also known as Fra-1) directly stimulated the transcription of miR-221/222, and the abundance of these miRNAs decreased with inhibition of MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase), placing miR-221/222 downstream of the RAS pathway. The miR-221/222-mediated reduction in E-cadherin abundance depended on their targeting of the 3' untranslated region (3'UTR) of TRPS1 (trichorhinophalangeal syndrome type 1), which is a member of the GATA family of transcriptional repressors. TRPS1 inhibited EMT by directly repressing expression of ZEB2 (Zinc finger E-box-binding homeobox 2). Therefore, miR-221/222 may contribute to the aggressive clinical behavior of basal-like breast cancers.
journal_name
Sci Signaljournal_title
Science signalingauthors
Stinson S,Lackner MR,Adai AT,Yu N,Kim HJ,O'Brien C,Spoerke J,Jhunjhunwala S,Boyd Z,Januario T,Newman RJ,Yue P,Bourgon R,Modrusan Z,Stern HM,Warming S,de Sauvage FJ,Amler L,Yeh RF,Dornan Ddoi
10.1126/scisignal.2002258subject
Has Abstractpub_date
2011-08-09 00:00:00pages
pt5issue
186eissn
1945-0877issn
1937-9145pii
scisignal.2002258journal_volume
4pub_type
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