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J Biol Chem. 2014 Aug 8;289(32):21888-95. doi: 10.1074/jbc.M114.582866. Epub 2014 Jun 25.

The microRNA-23b/27b/24 cluster promotes breast cancer lung metastasis by targeting metastasis-suppressive gene prosaposin.

Author information

1
From the Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544.
2
the Osteoncology and Rare Tumors Center, IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST IRCCS), Meldola 47014, Italy and.
3
From the Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, the Genomic Instability and Tumor Progression Program, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903 ykang@princeton.edu.

Abstract

MicroRNAs (miRNAs) have been shown to function as key regulators of tumor progression and metastasis. Recent studies have indicated that the miRNAs comprising the miR-23b/27b/24 cluster might influence tumor metastasis, although the precise nature of this regulation remains unclear. Here, expression of the miR-23b/27b/24 cluster is found to correlate with metastatic potential in mouse and human breast cancer cell lines and is elevated in metastatic lung lesions in human breast cancer patients. Ectopic expression of the miRNAs in the weakly metastatic mouse 4TO7 mammary tumor cell line had no effect on proliferation or morphology of tumor cells in vitro but was found to increase lung metastasis in a mouse model of breast cancer metastasis. Furthermore, gene expression profiling analysis of miRNA overexpressing 4TO7 cells revealed the direct targeting of prosaposin (PSAP), which encodes a secreted protein found to be inversely correlated with metastatic progression in human breast cancer patients. Importantly, ectopic expression of PSAP was able to suppress the metastatic phenotype in highly metastatic 4T1 and MDA-MB-231 SCP28 cells, as well as in cells ectopically expressing miR-23b/27b/24. These findings support a metastasis-promoting function of the miR-23b/27b/24 cluster of miRNAs, which functions in part through the direct inhibition of PSAP.

KEYWORDS:

Breast Cancer; Invasion; Metastasis; MicroRNA (miRNA); Tumor Metastases

PMID:
24966325
PMCID:
PMC4139207
DOI:
10.1074/jbc.M114.582866
[Indexed for MEDLINE]
Free PMC Article
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