Materials and Methods Useful For Affecting Tumor Cell Growth, Migration and Invasion

Abstract

It is disclosed herein that miR-221 and miR-222 down-regulate PTEN and TIMP3 tumor suppressors, resulting in TRAIL resistance. The present invention provides research, diagnostic, and therapeutic tools and methods related to this discovery. Diagnostics, prognostics and treatments for human hepatocellular cancer and non-small cell lung carcinoma having a TRAIL resistance are particularly described herein.

What is claimed is: 
     
         1 . A method to alter the TRAIL Expression Pattern in a cell, comprising altering c-Jun, miR-221 and miR-222 and PTEN or TIMP3 in a cell capable of expressing c-Jun, miR-221 and miR-222, PTEN and TIMP3, and altering TRAIL Expression Pattern. 
     
     
         2 . A method of  claim 1 , comprising inhibiting or overexpressing c-Jun, miR-221 and miR-222, PTEN or TIMP3 in a cell capable of expressing c-Jun, miR-221 and miR-222, PTEN and TIMP3. 
     
     
         3 . A method to alter gene expression in a TRAIL-resistant cell, comprising altering miR-221 and miR-222 in a cell that also expresses at least one nucleic acid selected from the group consisting of: c-Jun; PTEN and TIMP3; and altering gene expression in the TRAIL-resistant cell. 
     
     
         4 . A method of  claim 3 , comprising inhibiting or over-expressing miR-221 and miR-222 in a cell that also expresses at least one nucleic acid selected from the group consisting of: c-Jun; PTEN and TIMP3. 
     
     
         5 . A method of  claim 1 , wherein said cell is selected from the group consisting of: cancer cell; TRAIL-resistant cancer cell; non-small cell lung carcinoma; and hepatocellular carcinoma. 
     
     
         6 . A method to alter regulation of PTEN expression in a cell capable of expressing TIMP3 and miR-221 and miR-222, comprising altering miR-221 and miR-222 activity in a TIMP3-expressing and miR-221 and miR-222-expressing cell and altering regulation of TIMP3 expression. 
     
     
         7 . A method of  claim 6 , comprising over-expressing miR-221 and miR-222 in a cell that also expresses PTEN and inhibiting PTEN expression. 
     
     
         8 . A method of  claim 6 , comprising contacting a test cell with antisense miR-221 and anti-sense miR-222 and increasing PTEN expression.