miRNA PROFILING COMPOSITIONS AND METHODS OF USE

A method of treating breast cancer in a subject, comprising:

• a) analyzing tumor tissue obtained from a subject with breast cancer for the presence of metastatic or pro-metastatic breast cancer cells, by a method comprising identifying miRNA activity of one or more of let-7a, let-7d, let-7c, let-7i, miR-1, miR-100, miR-10a, miR-340, miR-15b, miR-186, miR-222, miR-182, miR-210, miR-193b, miR-26a, miR-27a, miR-29a, miR-27b, miR-29c, and miR-424 in a tissue of a subject;
• b) identifying metastatic or pro-metastatic cells as present in the tumor tissue if one or more of let-7a, let-7d, let-7c, let-7i, miR-1, miR-100, miR-10a, miR-340, miR-15b, miR-186, miR-222 is assessed as overexpressed in the tissue, or if one or more of miR-182, miR-210, miR-193b, miR-26a, miR-27a, miR-29a, miR-27b, miR-29c, and miR-424 is assessed as downregulated in the tissue, as compared to that of a control tissue;
• and
• c) treating the subject with an aggressive therapy for metastatic breast cancer when metastatic or pro-metastatic cells are identified.

A method of identifying metastatic or pro-metastatic cells in a tumor tissue of a subject with cancer, comprising:

• a) identifying miRNA activity of one or more miRNA known to be overexpressed or downregulated in metastatic or pro-metastatic cells, in tumor tissue of the subject, by delivering to the tumor tissue an effective amount of one or more nanosensors, comprising;
• i) a delivery particle comprising an iron oxide crystal coated with a polymer;
• and
• ii) a sensor oligonucleotide covalently attached to the polymer, comprising:
• A) a seed region comprising a nucleic acid sequence that is completely complementary to the miRNA and comprises a cleavage site which can be engaged by the miRNA and cleaved by the miRNA in complex with RNA induced silencing complex;
• B) two non-seed regions that each flank the seed region and are each comprised of nucleic acid sequences complementary to the miRNA to promote hybridization of the sensor oligonucleotide to the miRNA;
• and
• C) members of a quencher-fluorophore pair;
• and
• wherein the quencher fluorophore pair members respectively flank the cleavage site and are separated by a distance that permits quenching of emitted fluorescent signal;
• b) detecting fluorescence emitted from the one or more nanosensors and assessing if the activity of the miRNA(s) is higher or lower than that of a control tissue;
• and
• c) identifying metastatic or pro-metastatic cells as present in the tumor tissue if one or more of the miRNA is assessed as overexpressed or downregulated in the tissue.