Albumin production and cell proliferation
The present invention provides short activating RNA molecules which up-regulate albumin production. The present invention also provides methods of up-regulating albumin production, such methods involving the use of short activating RNA molecules capable of increasing the expression of albumin. The present invention also provides the use of the short activating RNA molecules in therapy, such as treating or preventing a hyperproliferative disorder and/or a disorder characterised by hypoalbuminemia.
1. A method of treating or preventing a hyperproliferative disorder and/or a disorder characterised by hypoalbuminemia, said method comprising administering to a subject in need thereof a short activating RNA which up-regulates albumin production, wherein said short activating RNA upregulates albumin production by activating a target gene, wherein the target gene is HNF4a, and wherein,
(i) said short activating RNA comprise a strand that is at least 95% complementary to a sequence located on the coding strand of the target gene between 500 nucleotides upstream and 500 nucleotides downstream of the transcription start site of the target gene, and
(ii) said short activating RNA comprises a sequence of at least 18 nucleotides.
2. The method according to claim 1 , wherein said hyperproliferative disorder is liver cancer or prostate cancer.
3. The method according to claim 1 , wherein said disorder characterised by hypoalbuminemia is cirrhosis, hepatitis or oedema.
4. The method according to claim 1 , wherein said short activating RNA molecule is a single or double stranded RNA molecule up to 30 nucleotides in length.
5. The method according to claim 4 , wherein said short activating RNA is a double stranded RNA molecule and comprises a number of unpaired nucleotides at the 3′ end of each strand forming 3′ overhangs.
6. The method according to claim 5 , wherein said 3′ overhang is UU or UUU.
7. The method according to claim 1 , wherein the short activating RNA inhibits cell proliferation.
8. A method according to claim 7 , wherein said cell is a hyperproliferative cell.
9. A method of treating or preventing a hyperproliferative disorder and/or a disorder characterised by hypoalbuminemia, said method comprising administering to a subject in need thereof a short activating RNA which up-regulates albumin production, wherein said short activating RNA upregulates albumin production by activating a target gene, wherein the target gene is HNF4a, and wherein said short activating RNA comprises a first strand having a sequence selected from SEQ ID NOs: 26, 28, 30, 32, 34 and 36.
10. The method according to claim 9 , wherein said short activating RNA comprises a second strand having a sequence selected from SEQ ID NO: 25, 27, 29, 31, 33 and 35.
11. The method according to claim 10 , wherein said short activating RNA comprises a number of unpaired nucleotides at the 3′ end of each strand forming 3′ overhangs.
12. The method according to claim 11 , wherein said 3′ overhang is UU or UUU.
13. The method according to claim 9 , wherein the short activating RNA inhibits cell proliferation.
14. A method according to claim 13 , wherein said cell is a hyperproliferative cell.