Differentially expressed microrna molecules for the treatment and diagnosis of cancer

Abstract

A significant challenge in cancer research field is to define molecular features that distinguish cancer stem cells from normal stem cells. In this study, microRNA (miRNA) expression profiles in human glioblastoma stem cells were compared to that of normal neural stem cells using combined microarray and deep sequencing analyses. These studies led to the identification of several miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. Characterizing the role of these miRNAs in glioblastoma stem cells is important for the development of miRNA-based therapies that specifically target tumor stem cells, but spare normal stem cells.

1 . A method of treating a cancer comprising:
 administering a therapeutically effective amount of a pharmaceutical composition to a subject having the cancer,   wherein the pharmaceutical composition comprises one or more therapeutic agents which target one or more miRNA molecules that is upregulated in cancer stem cells as compared to normal cells.   
     
     
         2 - 4 . (canceled) 
     
     
         5 . The method of claim  2 , wherein the one or more therapeutic agents includes at least one miRNA inhibitor that inhibits an upregulated miRNA molecule. 
     
     
         6 . The method of  claim 5 , wherein the upregulated miRNA is selected from miR-10a, miR-10b, miR-140-3p, miR-140-5p, miR-204, miR-424, miR-34a, miR-193a-3p, miR-455-5p, miR-455-3p, miR-9, miR-10a, miR-148a, miR-488, miR-196a1, miR-182, miR-96, miR-193b, miR-27a, miR-196b, miR-10b, miR-29b2, miR-23a, miR-107, miR-542-3p, miR-93, miR-365a4, miR-450a, miR-100, miR-105, miR-363, miR-105, miR-106b, miR-15b, miR-21, miR-376c, miR-93, miR-99b, miR-155, miR-33a, miR-876-3p, miR-362-3p, miR-25, let-7i, miR-423-3p, miR-34b, miR-16-2, miR-29a, miR-30d, miR-320, miR-181c, miR-128a, miR-21, let-7d, and miR-450b-5p. 
     
     
         7 . The method of  claim 1 , wherein the cancer is glioblastoma. 
     
     
         8 - 22 . (canceled) 
     
     
         23 . The method of  claim 5 , wherein the at inhibitor comprises a nucleic acid that is sufficiently complementary to the miRNA molecule to hybridize to the miRNA molecule under physiological conditions. 
     
     
         24 . The method of  claim 1 , further comprising administering to the subject at least one miRNA that is down regulated in a cancer stem cell as compared to a normal cell or an miRNA expression vector that overexpresses a downregulated miRNA molecule. 
     
     
         25 . The method of  claim 24 , wherein the downregulated miRNA molecule is selected from miR-371-5p, miR-1245, miR-335, miR-492, miR-874, miR-30b, miR-193a-5p, miR-602, miR-346, miR-663, miR-25, miR-219-5p6, miR-184, miR-135a7, miR-584, miR-665, miR-638, miR-503, miR-628-3p, miR-381, miR-78, miR-92b, miR-149, miR-135b, miR-302d, miR-498, miR-766, miR-1389, miR-623, miR-519c-5p, miR-182, miR-494, miR-129-5p10, miR-513-5p, miR-200b, miR-634, miR-654-5p, miR-518b, miR-658, miR-373, miR-30c-2, miR-130a, miR-557, miR-551a, miR-637, miR-518c, miR-525-5p, miR-596, miR-552, miR-625, miR-183, miR-187, miR-544, miR-891a, miR-519e, miR-933, miR-939, miR-214, miR-671-5p, miR-137, miR-92b, miR-525-3p, miR-19a, and miR-409-5p.