Compounds that target MYC microRNA responsive elements for the treatment of MYC-associated cancer
Novel mIR-330 agents and their methods of use are provided. Methods of treating MYC-associated cancers are provided.
1. A method of treating a MYC-associated cancer in a subject in need thereof, the method comprising:
selecting a subject that overexpresses MYC; and
administering to the subject a pharmaceutical composition comprising a nucleic acid sequence having at least 80% complementarity to a micro RNA (miR) Responsive Element (MRE) sequence set forth as SEQ ID NO:1, thereby treating cancer in the subject, wherein the MYC-associated cancer is further characterized by downregulation of hsa-miR-330-5p.
2. The method of claim 1 , wherein the nucleic acid sequence has at least 90% complementarity, 95% complementarity, or 98% complementarity to the MRE sequence set forth as SEQ ID NO:1.
3. The method of claim 1 , wherein the nucleic acid sequence is further perfectly complementary to an MRE seed sequence set forth as SEQ ID NO:2.
4. The method of claim 1 , wherein the nucleic acid sequence comprises a miRNA or an siRNA, optionally wherein the miRNA is a miR-330-5p compound.
5. The method of claim 4 , wherein the miRNA or siRNA is between 20 and 24 nucleotides in length.
6. The method of claim 1 , wherein the MRE is a MYC MRE.
7. The method of claim 1 , wherein MYC expression is downregulated in the subject after administering the pharmaceutical composition to the subject.
8. The method of claim 1 , wherein MYC mRNA cleavage is mediated or translation of MYC mRNA is inhibited.
9. The method of claim 1 , wherein the MYC-associated cancer is liver cancer or colorectal cancer.
10. The method of claim 1 , wherein the nucleic acid sequence is administered using a recombinant Adeno-Associated virus (AAV).
11. The method of claim 1 , wherein the nucleic acid sequence is a double-stranded nucleic acid sequence having a sense strand and an antisense strand, wherein the antisense strand has at least 80% complementarity to the MRE sequence.
12. A method of targeting MYC overexpression in a cancer cell characterized by overexpression of MYC, comprising contacting the cell with a nucleic acid sequence having at least 80% complementarity to an MRE sequence set forth as SEQ ID NO:1 to inhibit translation of the MYC mRNA, wherein the cancer cell is further characterized by downregulation of hsa-miR-330-5p.
13. The method of claim 12 , wherein the nucleic acid sequence comprises a miRNA or an siRNA, optionally wherein the miRNA is a miR-330-5p compound.