USE OF AN miRNA TO REDUCE PROLIFERATION OF A CANCER CELL

Abstract

A method is provided for decreasing at least one of the proliferation and the migration of a cancer cell comprising contacting a cancer cell with an effective amount of a pharmaceutically acceptable composition comprising a microRNA (miRNA) having a nucleotide sequence having at least 80% sequence similarity to the nucleotide sequence of miR-3189-3p derived from the miR-3189 mitron of the Growth Differentiation Factor 15 (GDF15) gene. The methods and compositions are advantageous for inhibiting proliferation and migration of, but not limited to, glioblastoma cells, melanoma cells, and breast cancer cells.

What is claimed: 
     
         1 . A method for decreasing at least one of the proliferation and the migration of a cancer cell comprising contacting a cancer cell with an effective amount of a pharmaceutically acceptable composition comprising a microRNA (miRNA), wherein said miRNA has a nucleotide sequence having at least 80% sequence similarity to the nucleotide sequence SEQ ID NO: 2, thereby decreasing at least one of the proliferation and migration of the cancer cell as compared to a control. 
     
     
         2 . The method of  claim 1 , wherein the cancer cell is a glial tumor cell, a melanoma cell, or a breast cancer cell. 
     
     
         3 . The method of  claim 2 , wherein the glial tumor cell is an astrocytoma tumor cell, an ependymal tumor cell, a glioblastoma multiforme tumor cell, or a primitive neuroectodermal tumor cell. 
     
     
         4 . The method of  claim 2 , wherein the glioblastoma multiforme is located in the brain or the spinal cord of the subject. 
     
     
         5 . The method of  claim 1 , wherein the miRNA reduces the expression of at least one of p63RoGEF and SF3B2 splicing factor in the cancer cell, or modulates the effect of MYC in the cancer cell. 
     
     
         6 . The method of  claim 1 , wherein the cancer cell is an isolated cancer cell, a cultured cell, a cell in a tissue of an animal or human patient, or progeny thereof. 
     
     
         7 . The method of any of  claim 1 , wherein the miRNA has a nucleotide sequence having at least 85%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to the nucleotide sequence of SEQ ID NO: 2. 
     
     
         8 . The method of  claim 7 , wherein the miRNA has a nucleotide sequence having at least 95%, sequence similarity to the nucleotide sequence SEQ ID NO: 2. 
     
     
         9 . The method of  claim 7 , wherein the miRNA has a nucleotide sequence having at least 97%, sequence similarity to the nucleotide sequence of SEQ ID NO: 2. 
     
     
         10 . The method of  claim 7 , wherein the miRNA has the nucleotide sequence of SEQ ID NO: 2. 
     
     
         11 . A method for treating a cancer comprising administering to an animal or human subject in need thereof an effective amount of a pharmaceutically acceptable composition comprising a microRNA (miRNA), wherein said miRNA has a nucleotide sequence having at least 80% sequence similarity to the nucleotide sequence of SEQ ID NO: 2, thereby decreasing at least one of the proliferation and migration of the cancer cell as compared to a control. 
     
     
         12 . The method of  claim 11 , wherein the cancer is a glial tumor, melanoma cell, or a breast cancer cell. 
     
     
         13 . The method of  claim 11 , wherein the glial tumor cell is an astrocytoma tumor cell, an ependymal tumor cell, a glioblastoma multiforme tumor cell, or a primitive neuroectodermal tumor cell. 
     
     
         15 . The method of  claim 11 , wherein the glioblastoma multiforme is located in the brain or the spinal cord of the subject. 
     
     
         16 . The method of  claim 11 , wherein the miRNA reduces the expression of at least one of p63RoGEF and SF3B2 splicing factor in the cancer cell, or modulates the effect of MYC in the cancer cell. 
     
     
         16 . The method of  claim 10 , wherein the miRNA has a nucleotide sequence having at least 85%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to the nucleotide sequence of SEQ ID NO: 2. 
     
     
         17 . The method of  claim 10 , wherein the miRNA has the nucleotide sequence of miR-3189-3p according to SEQ ID NO: 2. 
     
     
         18 . The method of  claim 10 , wherein the pharmaceutically acceptable composition is administered to the animal or human subject intravenously, subcutaneously, or intratumorally. 
     
     
         19 . The method of  claim 10 , wherein the pharmaceutically acceptable composition is formulated to deliver the miRNA across the blood-brain barrier or to deliver the miRNA as a nucleic acid expression product to the cells of the cancer. 
     
     
         20 . A composition comprising an oligonucleotide capable of hybridizing under physiological conditions to a nucleotide sequence that is the complement of the nucleotide sequence SEQ ID NO: 2, or the complement thereof, and in an amount effective to reduce at least one of the proliferation and the migration of a cancer cell in a patient administered said composition, and a pharmaceutically acceptable carrier. 
     
     
         21 . The composition of  claim 20 , wherein the oligonucleotide has a nucleotide sequence having at least 90% similarity to the nucleotide sequence SEQ ID NO: 2. 
     
     
         22 . The composition of  claim 20 , wherein the oligonucleotide has a nucleotide sequence SEQ ID NO: 2. 
     
     
         23 . The composition  claim 20 , wherein the composition further comprises a therapeutic agent therapeutically effective against the cancer cell. 
     
     
         24 . The composition of  claim 20 , wherein the cancer cell is a glioblastoma cell, a melanoma cell, or a breast cancer cell. 
     
     
         25 . A kit comprising at least one of: (a) reagents for preparation of samples from blood samples; (b) reagents for creating or synthesizing an miRNA oligonucleotide having at least 80% sequence similarity to the nucleotide sequence of SEQ ID NO: 2, wherein said reagents are in suitable container means, and wherein said reagents are packaged either in aqueous media or in lyophilized form, and instructions for employing the kit components for the synthesis or therapeutic use of the miRNA oligonucleotide in a patient in need thereof.