The Ohio State University

Muller Fabbri

Carlo M Croce

The present invention provides materials and methods related to the discovery that tumor secreted miR-21 and miR-29can function by binding as ligands to receptors of the Tolllike receptor family, murine TLR7 and human TLR8, in immune cells, triggering a TLR-mediated prometastatic inflammatory response, which leads to tumor growth and metastasis. Thus, by acting as paracrine agonists of TLRs, secreted miRNAs are key regulators of the tumor microenvironment. This mechanism of action of miRNAs is important in the tumor-immune system communication, in tumor growth and spread, and in cancer treatment.

Methods and compositions related to miR-21 and miR-29a, exosome inhibition, and cancer metastasis

Methods for restoring a desired pattern of DNA methylation, inducing re-expression of methylation-silenced tumor suppressor genes (TSGs), and/or inhibiting tumorigenicity both in vitro and in vivo in a subject in need thereof by administering an effective amount of one or more miR-29s sufficient to target one or more of DNMT3A and DNMT3B are disclosed.

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Los Angeles, CA, United States of America

Muller Fabbri