Abstract:
:The tumor suppressor p21 acts as a cell cycle inhibitor and has also been shown to regulate gene expression by functioning as a transcription corepressor. Here, we identified p21-regulated microRNAs (miRNAs) by sequencing small RNAs from isogenic p21(+/+) and p21(-/-) cells. Three abundant miRNA clusters, miR-200b-200a-429, miR-200c-141, and miR-183-96-182, were downregulated in p21-deficient cells. Consistent with the known function of the miR-200 family and p21 in inhibition of the epithelial-mesenchymal transition (EMT), we observed EMT upon loss of p21 in multiple model systems. To explore a role of the miR-183-96-182 cluster in EMT, we identified its genome-wide targets and found that miR-183 and miR-96 repressed common targets, including SLUG, ZEB1, ITGB1, and KLF4. Reintroduction of miR-200, miR-183, or miR-96 in p21(-/-) cells inhibited EMT, cell migration, and invasion. Conversely, antagonizing miR-200 and miR-183-96-182 cluster miRNAs in p21(+/+) cells increased invasion and elevated the levels of VIM, ZEB1, and SLUG mRNAs. Furthermore, we found that p21 forms a complex with ZEB1 at the miR-183-96-182 cluster promoter to inhibit transcriptional repression of this cluster by ZEB1, suggesting a reciprocal feedback loop.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Li XL,Hara T,Choi Y,Subramanian M,Francis P,Bilke S,Walker RL,Pineda M,Zhu Y,Yang Y,Luo J,Wakefield LM,Brabletz T,Park BH,Sharma S,Chowdhury D,Meltzer PS,Lal Adoi
10.1128/MCB.01043-13subject
Has Abstractpub_date
2014-02-01 00:00:00pages
533-50issue
3eissn
0270-7306issn
1098-5549pii
MCB.01043-13journal_volume
34pub_type
杂志文章abstract::Mouse mammary epithelial cells can be transformed in primary cultures to preneoplastic and neoplastic states when treated with N-methyl-N-nitrosourea (MNU). Mammary carcinomas arising from MNU-induced hyperplastic alveolar nodules (a type of mouse mammary preneoplastic lesion) contained transforming c-Ki-ras genes whe...
journal_title:Molecular and cellular biology
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
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pub_type: 杂志文章
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更新日期:2018-12-11 00:00:00