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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
Endogenous human microRNAs that suppress breast cancer metastasis
Sohail F Tavazoie1, Claudio Alarcón, Thordur Oskarsson
1Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Abstract:
A search for general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential. Here we show that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer cells in vivo. Of these microRNAs, miR-126 restoration reduces overall tumour growth and proliferation, whereas miR-335 inhibits metastatic cell invasion. miR-335 regulates a set of genes whose collective expression in a large cohort of human tumours is associated with risk of distal metastasis. miR-335 suppresses metastasis and migration through targeting of the progenitor cell transcription factor SOX4 and extracellular matrix component tenascin C. Expression of miR-126 and miR-335 is lost in the majority of primary breast tumours from patients who relapse, and the loss of expression of either microRNA is associated with poor distal metastasis-free survival. miR-335 and miR-126 are thus identified as metastasis suppressor microRNAs in human breast cancer.
Insights
Restoring microRNAs (miRNAs) like miR-126 and miR-335 in breast cancer cells can suppress metastasis. Loss of these miRNAs correlates with poor patient survival, identifying them as crucial metastasis suppressors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cancer metastasis remains a significant challenge in breast cancer treatment.
- Specific microRNAs (miRNAs) are downregulated as breast cancer cells acquire metastatic potential.
Purpose of the Study:
- To identify and characterize microRNAs that regulate cancer metastasis.
- To investigate the therapeutic potential of restoring specific miRNA expression in metastatic breast cancer.
Main Methods:
- Expression analysis of microRNAs in breast cancer cells with varying metastatic potential.
- In vivo studies to assess the effect of miRNA restoration on metastasis and tumor growth.
- Target gene identification and validation for miR-335.
Main Results:
- Restoring miR-126 and miR-335 expression in malignant cells suppressed lung and bone metastasis in vivo.
- miR-126 restoration reduced tumor growth and proliferation.
- miR-335 inhibited cancer cell invasion and migration by targeting SOX4 and tenascin C.
- Loss of miR-126 or miR-335 expression in primary tumors correlated with poor metastasis-free survival.
Conclusions:
- miR-126 and miR-335 function as critical metastasis suppressors in human breast cancer.
- Restoration of these miRNAs holds therapeutic promise for preventing breast cancer metastasis.
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