SiRNA TARGETING ETS1 AND ELK1 AND METHOD OF USING SAME IN THE INHIBITION OF CIP2A GENE IN CANCER TREATMENT
Disclosed are methods of attenuating activity of the gene promoter of CIP2A. siRNAs are used to target against Ets1 and Elk1 transcriptional factors, thereby blocking the binding of Ets1 and Elk1 to the CIP2A gene promoter. It is disclosed that the siRNAs targeted against Ets1 and Elk1 attenuate the gene expression of CIP2A. A kit containing siRNA reagents for attenuating the CIP2A gene expression is also disclosed.
1 . A pharmaceutical composition, comprising:
a) a first siRNA targeted against Ets1 mRNA, said first siRNA hybridizes to a target sequence of said Ets1 mRNA selected from the group consisting of SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 37;
b) a second siRNA targeted against Elk1 mRNA, said second siRNA hybridizes to a target sequence of said Elk1 mRNA selected from the group consisting of SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40 and SEQ ID NO: 41; and
c) a pharmaceutical acceptable carrier,
wherein said pharmaceutical composition inhibits gene expression of CIP2A in a cell.
2 . The pharmaceutical composition of claim 1 , wherein said first siRNA is at least one siRNA selected from the group consisting of SEQ ID NO: 30 and SEQ ID NO: 31.
3 . The pharmaceutical composition of claim 2 , wherein said first siRNA consists of SEQ ID NO: 30.
4 . The pharmaceutical composition of claim 2 , wherein said first siRNA consists of SEQ ID NO: 31.
5 . The pharmaceutical composition of claim 1 , wherein said second siRNA is at least one siRNA selected from the group consisting of SEQ ID NO: 32 and SEQ ID NO: 33.
6 . The pharmaceutical composition of claim 5 , wherein said second siRNA consists of SEQ ID NO: 32.
7 . The pharmaceutical composition of claim 5 , wherein said second siRNA consists of SEQ ID NO: 33.
8 . The pharmaceutical composition of claim 1 , wherein said first siRNA contains at least one modified nucleotide selected from the group consisting of 2′-O-methyl (2′OMe), 2′-deoxy-2′-fluoro (2′F), 2′-deoxy and 2′-O-(2-methoxyethyl) (MOE).
9 . The pharmaceutical composition of claim 2 , wherein said first siRNA contains at least one modified nucleotide selected from the group consisting of 2′-O-methyl (2′OMe), 2′-deoxy-2′-fluoro (2′F), 2′-deoxy and 2′-O-(2-methoxyethyl) (MOE).
10 . The pharmaceutical composition of claim 1 , wherein said second siRNA contains at least one modified nucleotide selected from the group consisting of 2′-O-methyl (2′OMe), 2′-deoxy-2′-fluoro (2′F), 2′-deoxy and 2′-O-(2-methoxyethyl) (MOE).
11 . The pharmaceutical composition of claim 5 , wherein said second siRNA contains at least one modified nucleotide selected from the group consisting of 2′-O-methyl (2′OMe), 2′-deoxy-2′-fluoro (2′F), 2′-deoxy and 2′-O-(2-methoxyethyl) (MOE).
12 . The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is suitable for oral administration.
13 . The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is suitable for injection administration.
14 . The injection administration of claim 13 , wherein said injection is intramuscular injection.