AIMP2-DX2 gene and SiRNA targeting AIMP2-DX2
The present invention relates to a variant of AIMP2 lacking exon 2 gene, named as AIMP2-DX2 gene, which is specifically expressed in cancer cells. The AIMP2-DX2 gene and siRNA targeting AIMP2-DX2 can be successfully used in the development of diagnosis and treatment of cancer.
1. An isolated siRNA (small interfering RNA) molecule comprising a sense region and an antisense region that down regulates expression of an AIMP2-DX2 gene via RNA interference (RNAi), wherein the sense region comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 27-154, and wherein the antisense region comprises a sequence that is complementary to a nucleotide sequence selected from the group consisting of SEQ ID NOs: 27-154, and wherein said siRNA does not down regulate expression of wild type AIMP2 via RNA interference.
2. The siRNA molecule of claim 1 , wherein the sense and antisense RNA strands forming the duplex region are covalently linked by a linker molecule.
3. The siRNA molecule of claim 1 , wherein the siRNA further comprises non-nucleotide material.
4. The siRNA molecule of claim 1 , wherein the linker molecule is a polynucleotide linker.
5. The siRNA molecule of claim 1 , wherein the linker molecule is a non-nucleotide linker.
6. A recombinant nucleic acid construct comprising a nucleic acid that is capable of directing transcription of a small interfering RNA (siRNA), the nucleic acid comprising: (a) at least one promoter; (b) a DNA polynucleotide segment that is operably linked to the promoter, (c) a linker sequence comprising at least 4 nucleotides operably linked to the DNA polynucleotide segment of (b); and (d) operably linked to the linker sequence a second polynucleotide, wherein the polynucleotide segment of (b) comprises a polynucleotide that is selected from the group consisting of SEQ ID Nos: 27-154, wherein the second polynucleotide of (d) comprises a polynucleotide that is complementary to at least one polynucleotide that is selected from the group consisting of SEQ ID Nos: 27-154.
7. The recombinant nucleic acid construct of claim 6 , wherein the linker sequence comprises at least 9 nucleotides.
8. The recombinant nucleic acid construct of claim 6 comprising at least one transcriptional terminator that is operably linked to the DNA polynucleotide segment.
9. The recombinant nucleic acid construct of claim 6 , which comprises SEQ ID NO: 13 and SEQ ID NO: 26.
10. An isolated host cell transformed or transfected with the recombinant nucleic acid construct of claim 6 .
11. A pharmaceutical composition for treating cancer, which comprises (a) the siRNA of claim 1 as an active ingredient; and (b) a pharmaceutically acceptable carrier.
12. A pharmaceutical composition for treating cancer, which comprises (a) the recombinant nucleic acid construct of claim 6 as an active ingredient; and (b) a pharmaceutically acceptable carrier.