Ras-regulated microRNAs as a novel anti-cancer therapeutic strategy

Abstract (Set) MicroRNAs (miRNAs) are 18-24 nucleotide RNA molecules that regulate the stability or translational efficiency of target mRNAs. miRNAs are frequently dysregulated in cancer cells and can act as both oncogenes and tumor-suppressors. It is estimated that there are approximately 37,170 new cases of, 33,370 deaths due to, and $1.5 billion spent on treatment of pancreatic cancer in the United States each year. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies and mutational activation of the KRAS2 oncogene occurs in over 90% of these cases. JHU scientists have identified a set of miRNA transcription units some that have increased expression by oncogenic Kras signaling and some that have decreased expression due to Kras signaling. They have further shown that specific miRNAs that are repressed by Ras are expressed at low levels in human PDAC cells. Restoration of expression of these miRNAs in PDAC cells dramatically inhibits anchorage-independent growth and completely blocks the ability of these cells to form tumors in mice. Delivery of miRNAs or mimics of miRNAs that are repressed by Ras signaling therefore represents a promising strategy for cancer therapy. Similarly, inhibition of miRNAs that are induced by Ras may also be effective. Description (Set) ? miRNAs regulated by a key oncogene ? miRNA exhibits tumor suppressor activity ? potential anti-cancer therapeutic Proposed Use (Set) MicroRNAs and inhibitors of miRNAs as anti-cancer therapeutic agents

Inventor(s): Mendell, Joshua ,Kent, Oliver,Maitra, Anirban

Type of Offer: Licensing



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