Methods and compositions using miR-3151 in the diagnosis and treatment of cancer
Compositions comprising therapeutic oligonucleotide miR-3151 compounds that target the expression of genes associated with tumorigenesis or cell transformation are provided.
1. A method of treating a subject having a cancer having an increased expression of miR-3151, the method comprising:
administering to the subject an effective amount of a miR-3151 inhibitor sufficient to decrease expression of miR-3151, wherein the level of miR-3151 is decreased after administration, thereby treating the subject;
wherein the cancer is melanoma having a BRAF mutation.
2. The method of claim 1 wherein the miR-3151 inhibitor is an antagomiR.
3. The method of claim 1 , further comprising: administering a proteasome inhibitor.
4. The method of claim 3 , wherein the proteasome inhibitor is selected from the group consisting of: bortezomib, disulfiram, epigallocatechin-3-gallate, salinosporamide A, carfilzomib, and epoxomicin.
5. The method of claim 1 , wherein the miR-3151 inhibitor comprises an oligonucleotide, wherein the oligonucleotide has a nucleobase sequence having at least 90% complementarity to: SEQ ID NO 37.
6. The method of claim 1 wherein the subject is a human.
7. A method of treating a subject having a cancer having an increased expression of miR-3151, comprising:
measuring the expression of at least one biomarker in a biological sample from the subject, wherein the at least one biomarker is selected from the group consisting of: gene products of BAALC and miR-3151;
comparing the expression of the at least one biomarker to a corresponding control;
determining whether the expression of either BAALC or miR-3151 is high;
administering the miR-3151 inhibitor if the expression of either BAALC or miR-3151 is high; in an amount sufficient to modulate expression of one or more of BAALC and miR-3151;
wherein the levels of one or more of BAALC and miR-3151 are decreased after administration, thereby treating the subject; wherein the cancer is melanoma having a BRAF mutation.
8. The method of claim 7 , further comprising: monitoring the expression of the at least one biomarker subsequent to the step of administering the miR-3151 inhibitor.
9. The method of claim 7 , wherein the miR-3151 inhibitor is an antagomiR.
10. The method of claim 7 , further comprising: administering a proteasome inhibitor.
11. The method of claim 10 , wherein the proteasome inhibitor is selected from the group consisting of: bortezomib, disulfiram, epigallocatechin-3-gallate, salinosporamide A, carfilzomib, and epoxomicin.
12. The method of claim 7 , wherein the miR-3151 inhibitor comprises an oligonucleotide, wherein the oligonucleotide has a nucleobase sequence having at least 90% complementarity to: SEQ ID NO 37.
13. The method of claim 7 , wherein the subject is a human.