Use of miR-494 to Modulate TRAIL-induced Apoptosis through BIM Down-regulation

Abstract

Methods and compositions for inhibiting tumorigenicity both in vitro and in vivo in a subject in need thereof, comprising administering an effective amount of an anti-miR-494 nucleic acid construct sufficient to target one or more tumor suppressor genes (TSGs) are described. Activation of the ERK1/2 pathway is a major determinant of diverse cellular processes and cancer development and is responsible for the transcription of several important miRNAs. Described herein is a link between the ERK1/2 pathway and BIM expression through miR-494. This ERK1/2 pathway regulates apoptosis and cell proliferation through miR-494 and mechanisms responsible for TRAIL resistance. Materials and methods related to the study and treatment of cancer are described.

What is claimed is: 
     
         1 . A method of affecting a cell by inhibiting proliferation of the cell and/or inducing apoptosis of the cell, the method comprising introducing an effective amount of a miR-specific inhibitor of at least miR-494 into a cell in need thereof. 
     
     
         2 . The method of  claim 1 , wherein the miR-specific inhibitor comprises a nucleotide sequence of least 6 consecutive nucleotides that are complementary to the miR-494, and has at least 50% complementarity to the rest of the miR-494 sequence, and wherein the miR-specific inhibitor of miR-494 induces expression of at least one of BIM and TRAIL in the cell. 
     
     
         3 . The method of  claim 1 , wherein the miR-specific inhibitor is selected from the group consisting of anti-miRs and target mimics. 
     
     
         4 . The method of  claim 1 , wherein the cell is selected a cancer cell.