Diagnostic, prognostic and therapeutic uses of long non-coding RNAs for cancer and regenerative medicine
Long non-coding RNAs (lncRNAs) and methods of using them diagnostically and therapeutically for treatment of cancer, stem cell therapy, or regenerative medicine are disclosed. In particular, the invention relates to lncRNAs that play roles in regulation of genes involved in cell proliferation, differentiation, and apoptosis. Such lncRNAs can be used as biomarkers to monitor cell proliferation and differentiation during cancer progression or tissue regeneration. One of the identified lncRNAs, referred to as PANDA (a P21-Associated NcRNA, DNA damage Activated), inhibits the expression of apoptotic genes normally activated by the transcription factor NF-YA. Inhibitors of PANDA sensitize cancerous cells to chemotherapy and can be used in combination with chemotherapeutic agents for treatment of cancer.
1. A composition comprising one or more PANDA inhibitors, wherein the one or more PANDA inhibitors are selected from the group consisting of a small interfering RNA (siRNA), a microRNA (miRNA), a Piwi-interacting RNA (piRNA), a small nuclear RNA (snRNA), and an antisense oligonucleotide.
2. The composition of claim 1 comprising at least one siRNA comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS:12-14.
3. The composition of claim 1 , further comprising a pharmaceutically acceptable excipient.
4. A method for treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a chemotherapeutic agent in combination with a therapeutically effective amount of the composition of claim 3 .
5. The method of claim 4 , wherein the composition comprises an siRNA comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS:12-14.
6. The method of claim 4 , wherein the chemotherapeutic agent is selected from the group consisting of doxorubicin, daunorubicin, valrubicin, idarubicin, and epirubicin.
7. The method of claim 6 , wherein the chemotherapeutic agent is doxorubicin.
8. The method of claim 4 , wherein the cancer is breast cancer.
9. The method of claim 8 , wherein the cancer is breast metastatic ductal carcinoma.
10. The method of claim 4 , wherein multiple cycles of treatment are administered to the subject for a time period sufficient to effect at least a partial tumor response.
11. The method of claim 4 , wherein multiple cycles of treatment are administered to the subject for a time period sufficient to effect a complete tumor response.
12. A method for inhibiting PANDA in a subject comprising administering an effective amount of the composition of claim 3 to the subject.
13. The method of claim 12 , wherein the inhibitory RNA molecule is an siRNA comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS:12-14.
14. A kit comprising the composition of claim 3 .
15. The kit of claim 14 , further comprising one or more chemotherapeutic agents.