MiR-137 targets estrogen-related receptor alpha and impairs the proliferative and migratory capacity of breast cancer cells.

Abstract

ERRα is an orphan nuclear receptor emerging as a novel biomarker of breast cancer. Over-expression of ERRα in breast tumor is considered as a prognostic factor of poor clinical outcome. The mechanisms underlying the dysexpression of this nuclear receptor, however, are poorly understood. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play important roles in tumor initiation and progression. In the present study, we have identified that the expression of ERRα is regulated by miR-137, a potential tumor suppressor microRNA. The bioinformatics search revealed two putative and highly conserved target-sites for miR-137 located within the ERRα 3'UTR at nt 480-486 and nt 596-602 respectively. Luciferase-reporter assay demonstrated that the two predicted target sites were authentically functional. They mediated the repression of reporter gene expression induced by miR-137 in an additive manner. Moreover, ectopic expression of miR-137 down-regulated ERRα expression at both protein level and mRNA level, and the miR-137 induced ERRα-knockdown contributed to the impaired proliferative and migratory capacity of breast cancer cells. Furthermore, transfection with miR-137 mimics suppressed at least two downstream target genes of ERRα-CCNE1 and WNT11, which are important effectors of ERRα implicated in tumor proliferation and migration. Taken together, our results establish a role of miR-137 in negatively regulating ERRα expression and breast cancer cell proliferation and migration. They suggest that manipulating the expression level of ERRα by microRNAs has the potential to influence breast cancer progression.

• Authors: Yuanyin Zhao, Yuping Li, Guiyu Lou, Li Zhao, Zhizhen Xu, Yan Zhang, Fengtian He
• Journal: PloS one (PLoS One) Vol. 7 Issue 6 Pg. e39102 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22723937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• CCNE1 protein, human
• Cyclin E
• ERRalpha estrogen-related receptor
• MIRN137 microRNA, human
• MicroRNAs
• Oncogene Proteins
• RNA, Messenger
• Receptors, Estrogen

Topics

• 3' Untranslated Regions
• Base Sequence
• Binding Sites
• Breast Neoplasms (genetics, metabolism)
• Cell Cycle Checkpoints (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Cyclin E (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs (genetics, metabolism)
• Oncogene Proteins (genetics, metabolism)
• RNA Interference
• RNA, Messenger (chemistry, genetics)
• Receptors, Estrogen (genetics, metabolism)
• Signal Transduction