Endogenous human microRNAs that suppress breast cancer metastasis

Nature. 2008. 451:147-52.

Speaker: 沈郁婷                                             Date:2007/10/03 14:10~15:00

Commentator: 呂佩融 老師                           Place: Room 601

Abstract:

Metastasis is a important question in solid tumours, but our understanding of its molecular and cellular determinants is limited. Transcription has revealed sets of genes, or ‘signatures’, for which expression in primary tumours correlates with metastatic relapse or poor survival. How could the mechanism regulate these genes which endow cancer cells with a more invasive phenotype, enhanced angiogenic and intravasation activity ? MicroRNAs are attractive candidates as upstream regulators of metastatic progression because microRNAs can posttranscriptionally regulate entire sets of genes. MicoRNAs are a category of naturally occurring RNA molecules that play important regulatory roles in plants and animals by targeting mRNAs for cleavage or translational repression. In this paper, Sohail F. Tavazoie focused on the three microRNAs: miR-335, miR-126, miR-206 whose expression was most decreased in metastatic cells. They restored expression of miR-335, miR-126 or miR-206 in breast cancer cells and suppressed lung and bone metastasis. These three microRNAs suppressed tumor through different mechanisms: miR-126 reduced tumor growth and proliferation, whereas miR-335 and miR-206 regulated migration and morphology. Then, the authors identified putative metastasis genes that miR-335 suppresses, they found miR-335 suppress the progenitor cell transcription factor SOX4 and extracellular matrix component tenascin C expression through targeting of 3’UTRs of these genes. This reasearch identified microRNAs as clinically meaningful suppressors of metastasis.

References:

1. Lower AJ et al. lMicroRNAs as prognostic indicators and therapeutic targets: potential effect on breast cancer management. Clin Cancer Res. 14:360-5 (2008)