5-halouracil-modified microRNAs and their use in the treatment of cancer
The present disclosure provides nucleic acid compositions that incorporate one or more halouracil molecules. More specifically, the present disclosure reveals that the replacement of uracil nucleotides within a microRNA nucleotide sequence with a 5-halouracil increases the ability of the micro-RNA to inhibit cancer progression and tumorigenesis. As such, the present disclosure provides various nucleic acid (e.g., microRNA) compositions having 5-halouracil molecules incorporated in their nucleic acid sequences and methods for using the same. The present disclosure further provides pharmaceutical compositions comprising the modified nucleic acid compositions, and methods for treating cancers using the same.
1. A method for treating breast cancer comprising administering to a subject an effective amount of a modified microRNA having a nucleotide sequence CGACGGCAU F AU F ACACU F ACAGU F G [SEQ ID NO. 32], wherein said subject has been diagnosed with breast cancer, and wherein progression of said breast cancer is inhibited by the administration of the modified microRNA nucleic acid composition, wherein said breast cancer is triple negative breast cancer.
2. The method of claim 1 , wherein said subject is a human.
3. The method of claim 2 , wherein the modified microRNA nucleic acid binds to a complementary portion of the MDC1 3′UTR nucleotide sequence set forth in SEQ ID NO: 33.
4. The method of claim 2 , wherein said modified microRNA nucleic acid composition is administered to the subject by injection.
5. A method for treating breast cancer comprising administering to a subject an effective amount of a modified microRNA consisting of a nucleotide sequence CGACGGCAU F AU F ACACU F ACAGU F G [SEQ ID NO. 32], wherein said subject has been diagnosed with breast cancer, and wherein progression of said breast cancer is inhibited by the administration of the modified microRNA nucleic acid composition.
6. The method of claim 5 , wherein said subject is a human.
7. The method of claim 6 , wherein said breast cancer is selected from the group of triple negative breast cancer, ductal carcinoma and lobular carcinoma.
8. The method of claim 7 , wherein said breast cancer is triple negative breast cancer.
9. The method of claim 6 , wherein the modified microRNA nucleic acid binds to a complementary portion of the MDC1 3′UTR nucleotide sequence set forth in SEQ ID NO: 33.
10. The method of claim 6 , wherein said modified microRNA nucleic acid composition is administered to the subject by injection.