MicroRNA-495 mimics delivery inhibits lung tumor progression.

ABSTRACT

MicroRNAs (miRNAs) can function as tumor suppressors and might provide an efficient strategy for annihilating cancer. Specific miRNAs can be reintroduced into tumor cells to elicit the tumor suppressor activities. We show that systemically delivered, synthetic miRNA mimics in complex with a novel neutral lipid emulsion are preferentially targeted to lung tumors and show therapeutic benefit in mouse models of lung cancer. The delivery was demonstrated using mimics of the tumor suppressor microRNA-495 which is found downregulated in most lung cancer. Systemic treatment of a Kras-activated autochthonous mouse model of non-small cell lung cancer (NSCLC) led to a significant decrease in tumor burden. Specifically, mice treated with microRNA-495 displayed a large reduction in tumor area compared to mice treated with a miRNA control. These findings provide direct evidence that systematically delivered synthetic miRNA mimics to the mammalian lung can inhibit tumor proliferation and support the promise of miRNAs as a targeted therapy for lung cancer in future.