Neurotensin-induced tumor formation is regulated by micro rna 133a-aftiphilin-dependent receptor recycling

Abstract

This application discloses methods of treating, preventing, and diagnosing colorectal cancer and IBD in a subject comprising administering an effective dose of antisense miR-133α or AFTPH to the subject or detecting expression levels of miR-133α and AFTPH.

1 . A method of treating colorectal cancer or inflammatory bowel disease in a subject, the treatment comprising administering an effective dose of antisense miR-133α. 
     
     
         2 . (canceled) 
     
     
         3 . A method of diagnosing colorectal cancer or inflammatory bowel disease in a subject wherein an increased expression of miR-133α is detected, wherein the increased expression of miR-133α compared to a control subject is indicative of the presence of colorectal cancer or inflammatory bowel disease or the likelihood of the colorectal cancer or inflammatory bowel disease progressing. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the antisense miR-133α is administered intracolonically. 
     
     
         6 . The method of  claim 1 , wherein the antisense miR-133α is expressed by a lentivirus. 
     
     
         7 . The method of  claim 6 , wherein the antisense miR-133α expressing lentivirus is administered intravenously. 
     
     
         8 . The method of  claim 1 , wherein the antisense miR-133α is a locked nucleic acid based miR-133α. 
     
     
         9 . The method of  claim 8 , wherein the locked nucleic acid based miR-133α is administered intracolonically. 
     
     
         10 . The method of  claim 1 , wherein the colorectal cancer is a cancer selected from a group comprising carcinomas, adenomatous polyps, adenocarcinomas, colonic carcinoids, colonic polyps, colorectal callous ademomas, colon cancer, bowel cancer, rectal cancer, carcinoid tumors, gastrointestinal stromal tumors, and lymphyomas. 
     
     
         11 . The method of  claim 1 , wherein the inflammatory bowel disease is selected from a group comprising Crohn's disease, ulcerative colitis, colitis, collagenous colitis, lymphocytic colitis, ischaemic colitis, diversion colitis, Behcet's disease, and indeterminate colitis. 
     
     
         12 . A method of treating colorectal cancer or inflammato bowe disease in a subject, the treatment comprising administering an effective dose of a AFTPH polypeptide. 
     
     
         13 . (canceled) 
     
     
         14 . A method of diagnosing colorectal cancer or inflammatory bowel disease in a subject wherein a decreased expression of AFTPH is detected, wherein the decreased expression of AFTPH compared to a control subject is indicative of the presence of colorectal cancer or inflammatory bowel disease or the likelihood of the colorectal cancer or inflammatory bowel disease progressing. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 12 , wherein the AFTPH polypeptide is expressed by a lentivirus. 
     
     
         17 . The method of  claim 12 , wherein the AFTPH polypeptide is administered intracolonically or intravenously. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 16 , wherein the lentivirus expressing AFTPH polypeptide is administered intravenously. 
     
     
         20 . The method of  claim 12 , wherein the AFTPH polypeptide is a modified AFTPH polypeptide. 
     
     
         21 . The method of  claim 20  wherein the modified AFTPH polypeptide is administered by direct administration to a tumor. 
     
     
         22 . The method of  claim 20  wherein the modified AFTPH polypeptide is administered intravenously or intraperitoneally. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 12 , wherein the colorectal cancer is a cancer selected from a group comprising carcinomas, adenomatous polyps, adenocarcinomas, colonic carcinoids, colonic polyps, colorectal callous ademomas, colon cancer, bowel cancer, rectal cancer, carcinoid tumors, gastrointestinal stromal tumors, and lymphomas. 
     
     
         25 . The method of  claim 12  wherein the irritable bowel syndrome disease is selected from a group comprising Crohn's disease, ulcerative colitis, colitis, collagenous colitis, lymphocytic colitis, ischaemic colitis, diversion colitis, Behcet's disease, and indeterminate colitis. 
     
     
         26 . The method of  claim 1 , wherein the subjectis a mammal. 
     
     
         27 . The method of  claim 26 , wherein the subject is a human.