Use of hepatitis B X-interacting protein (HBXIP) in modulation of apoptosis
Novel methods of regulating cellular apoptosis by affecting the interaction of hepatitis B X-interacting protein (HBXIP) with Survivin are described. More specifically, these novel methods of enhancing apoptosis of neoplastic cells comprises inhibiting interaction of hepatitis B X-interacting protein (HBXIP) with Survivin using siRNA or antisense compounds.
1. An isolated nucleic acid molecule that inhibits interaction of Survivin with hepatitis B X-interacting protein (HBXIP), wherein the nucleic acid molecule comprises an antisense nucleic acid molecule or siRNA molecule that inhibits expression of HBXIP, wherein the nucleic acid molecule comprises at least a 15 nucleotide fragment of SEQ ID NO: 7 or complement thereof, but not more than 30 nucleotides.
2. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises a modified backbone.
3. The isolated nucleic acid molecule of claim 2 , wherein the modified backbone comprises phosphorothioates.
4. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule has greater than 90% identity with a nucleic acid molecule encoding the HBXIP.
5. The isolated nucleic acid molecule of claim 4 , wherein the HBXIP is encoded by the nucleic acid sequence of SEQ ID NO: 3.
6. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises an antisense molecule.
7. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises an siRNA molecule.
8. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises one or more substituted sugar moieties.
9. A pharmaceutical composition comprising:
a) a nucleic acid molecule that inhibits interaction of Survivin with hepatitis B X-interacting protein (HBXIP), wherein the nucleic acid molecule comprises an antisense nucleic acid molecule or siRNA molecule that inhibits expression of HBXIP, wherein the nucleic acid molecule comprises at least a 15 nucleotide fragment of SEQ ID NO: 7 or complement thereof, but is not more than 30 nucleotides; and
b) a pharmaceutically acceptable carrier.
10. The pharmaceutical composition of claim 9 , wherein the nucleic acid molecule comprises a modified backbone.
11. The pharmaceutical composition of claim 10 , wherein the modified backbone comprises phosphorothioates.
12. The pharmaceutical composition of claim 9 , wherein the nucleic acid molecule has greater than 90% identity with a nucleic acid molecule encoding the HBXIP.
13. The pharmaceutical composition of claim 12 , wherein the HBXIP is encoded by the nucleic acid sequence of SEQ ID NO: 3.
14. The pharmaceutical composition of claim 9 , wherein the nucleic acid molecule comprises an antisense molecule.
15. The pharmaceutical composition of claim 9 , wherein the nucleic acid molecule comprises an siRNA molecule.
16. The pharmaceutical composition of claim 9 , wherein the nucleic acid molecule comprises one or more substituted sugar moieties.
17. The pharmaceutical composition of claim 15 , wherein the siRNA molecule comprises a sense strand encoded by a nucleic acid sequence as shown in SEQ ID NO: 7.
18. The pharmaceutical composition of claim 15 , wherein the siRNA molecule comprises an antisense strand encoded by a nucleic acid sequence as shown in SEQ ID NO: 8.
19. The isolated nucleic acid molecule of claim 7 , wherein the siRNA molecule comprises a sense strand encoded by a nucleic acid sequence as shown in SEQ ID NO: 7.
20. The isolated nucleic acid molecule of claim 7 , wherein the siRNA molecule comprises an antisense strand encoded by a nucleic acid sequence as shown in SEQ ID NO: 8.
21. An siRNA molecule that inhibits interaction of Survivin with hepatitis B X-interacting protein (HBXIP) by inhibiting expression of HBXIP, wherein the siRNA molecule comprises a sense strand encoded by a nucleic acid sequence as shown in SEQ ID NO: 7.
22. An siRNA molecule that inhibits interaction of Survivin with hepatitis B X-interacting protein (HBXIP) by inhibiting expression of HBXIP, wherein the siRNA molecule comprises an antisense strand encoded by a nucleic acid sequence as shown in SEQ ID NO: 8.