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

ABSTRACT: ERR? is an orphan nuclear receptor emerging as a novel biomarker of breast cancer. Over-expression of ERR? 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 ERR? 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 ERR? 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 ERR? expression at both protein level and mRNA level, and the miR-137 induced ERR?-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 ERR?-CCNE1 and WNT11, which are important effectors of ERR? implicated in tumor proliferation and migration. Taken together, our results establish a role of miR-137 in negatively regulating ERR? expression and breast cancer cell proliferation and migration. They suggest that manipulating the expression level of ERR? by microRNAs has the potential to influence breast cancer progression.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC3377602 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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

Zhao Yuanyin Y Li Yuping Y Lou Guiyu G Zhao Li L Xu Zhizhen Z Zhang Yan Y He Fengtian F

PloS one 20120618 6

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 ...[more]

PMID: 22723937

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Dataset Information

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

Publications

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

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