miR-21 is a microRNA that inhibits the translation of PDCD4, TPM1, maspin and PTEN mRNAs in breast, brain, lung, and pancreatic cancers. miR-17 is another oncogenic microRNA that suppresses the translation of anti-proliferative p21 as well as proapoptotic Bim and PTEN mRNAs. We hypothesize that inhibition of miR-21 or miR-17 by a complementary oligonucleotide in breast cancer cells via receptor-mediated endocytosis will restore tumor suppressor proteins and reduce breast cancer cell proliferation, invasion and metastasis. With a complementary locked nucleic acid (LNA) transfected into breast cancer cells, we have validated 95�1% knockdown of endogenous miR-21. Most breast cancer cells overexpress insulin-like growth factor 1 (IGF1) receptor. We are currently targeting miR-21 and miR-17 by introducing sequence-specific peptide nucleic acid (PNA) 12-mers conjugated to a C-terminal IGF1 analog, because we have previously shown that PNA-IGF1 analogs are endocytosed specifically into breast cancer cells. Supported by NIH 1 R44 CA136306 and CA148565.

Directing miRNA-regulatory PNAs to breast cancer cells with synthetic targeting peptides

244th National Meeting (2012)

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