Tap63 regulated oncogenic long non-coding rnas
AssigneeH. Lee Moffitt Cancer Center and Research Institute, Inc.
InventorsElsa R. FLORES, Marco NAPOLI
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Abstract
Disclosed herein are 2 novel long non-coding RNAs (lncRNAs), TROLL-2 and TROLL-3. It is shown herein that lncRNAs TROLL-2 and TROLL-3, as well as their effector WDR26, are suitable targets for cancer therapies and can be used to make prognostic determinations about a cancer and determine if immune checkpoint inhibitors should be used to treat a cancer.
Claims23
A method of assessing tumor grade and/or progression of a cancer and/or metastasis or detecting the presence of a cancer in a subject comprising obtaining a tissue sample from a subject and measuring the expression level of the long non-coding RNA for TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8 and/or expression level of WDR26;
- wherein the higher the level of lncRNA for TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8 and/or the higher the level of WDR26 and/or NCOA5 and/or the more WDR26 and/or NCOA5 localized in the cytoplasm of a cell relative to a control, the greater the severity and/or invasiveness of the tumor is indicated;
- or wherein the presence of lncRNA for TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8 indicates the presence of a cancer in the tissue sample from the subject.
A method of assessing the efficacy of a cancer treatment regimen administered to a subject comprising obtaining a tissue sample from a subject and measuring the expression level of the long non-coding RNA for TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8;
- and/or measuring the expression level of WDR26 and/or NCOA5;
- and/or measuring the intracellular localization of WDR26 and/or NCOA5 relative to a control;
- wherein when the expression level of lncRNA for TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8 and/or the expression level of WDR26 and/or NCOA5 is i) higher than a negative control, ii) equivalent to or has not decreased relative to a positive control, and/or iii) wherein the cytoplasmic localization of WDR26 and/or NCOA5 is greater than a negative control and/or equivalent to or has not decreased relative to a positive control indicates that the treatment regimen is not efficacious;
- preferably wherein the positive control is a reference gene or pretreatment sample from the subject whose cancer treatment regimen is being assessed.
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A method of treating a cancer in a subject comprising obtaining a tissue sample from a subject receiving a cancer treatment regimen and measuring the expression level of the long non-coding RNA for TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8;
- and/or measuring the expression level of WDR26 and/or NCOA5;
- and/or measuring the intracellular localization of WDR26 and/or NCOA5 relative to a control;
- wherein when the expression level of lncRNA for TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8 and/or the expression level of WDR26 and/or NCOA5 is i) higher than a negative control, ii) equivalent to or has not decreased relative to a positive control, and/or iii) wherein the cytoplasmic localization of WDR26 and/or NCOA5 is greater than a negative control and/or equivalent to or has not decreased relative to a positive control;
- indicates that the treatment regimen is not efficacious;
- and wherein the method further comprises changing the treatment regimen when the treatment regimen is not efficacious.
A method of treating a cancer in a subject comprising i) obtaining a tissue sample from the subject;
- ii) assaying the tissue sample for the presence and/or expression level of the long non-coding RNA for TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8;
- wherein the presence of lncRNA for TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8 indicates the presence of a cancer in the tissue sample from the subject;
- and iii) administering to a subject positive for TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8 an anti-cancer agent and/or immunotherapy.
A method of screening for a potential anti-cancer agent comprising contacting a cancer cell with the anti-cancer agent and measuring expression levels of TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8;
- wherein decreased expression of TROLL-1, TROLL-2, TROLL-3, TROLL-5, TROLL-7, and/or TROLL-8 indicates that the potential anti-cancer agent reduces cancer or measuring expression levels of WDR26 and/or NCOA5 wherein decreased expression of WDR26 and/or NCOA5 indicates that the potential anti-cancer agent reduces cancer.
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A kit for the detection, diagnosis, and/or prognosis of a cancer comprising any of the primers of Table 3 and/or Table 5.
Dependencies are inferred from the claim text.