Breast cancer metastasis: a microRNA story.
MicroRNAs (miRNAs) are small noncoding RNAs with regulatory functions, which play an important role in breast cancer. Several studies have shown that miRNAs can act either as tumor suppressors or as oncogenes, and that measurement of miRNA expression in malignancies may have diagnostic and prognostic implications. This article highlights a series of three recent studies that prove the involvement of miRNAs in breast cancer metastases. The first proves that miR-10b indirectly activates the pro-metastatic gene RHOC by suppressing HOXD10, thus leading to tumor invasion and metastasis. The second proves that miR-373 and miR-520c can also promote tumor invasion and metastasis, at least in part by regulating the gene CD44. The third identifies miR-335, miR-206, and miR-126 as suppressors of breast cancer metastasis. Loss of miR-335 leads to the activation of SOX4 and TNC (encoding tenascin C), which are responsible for the acquisition of metastatic properties. Altogether, these remarkable findings are important for our understanding of malignant transformation in the breast and may have implications for the management of patients with advanced breast cancer. The use of miRNAs as anticancer therapeutic agents is promising, and such fine molecular studies certainly help in bringing miRNAs closer to clinical practice.
Negrini
Massimo
M
Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, via Luigi Borsari, Ferrara 44100, Italy.
Calin
George Adrian
GA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006609:High Mobility Group Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D055751:SOXC Transcription Factors; D019063:Tenascin / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D018631:ras Proteins / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics; D000075024:rhoC GTP-Binding Protein
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; C490944:Hoxd10 protein, mouse; D035683:MicroRNAs; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse; D019063:Tenascin; D015534:Trans-Activators; D014157:Transcription Factors; C072064:HOXD10 protein, human; C066690:RHOC protein, human; C512911:Rhoc protein, mouse; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein