MicroRNA-Based Methods and Assays for Osteosarcoma

Abstract

Provided are methods and compositions useful in the diagnosis, treatment, and monitoring of osteosarcoma. Antisense to certain microRNA (miRNA) found to be associated with cancer stem cells (CSCs) or tumor-initiating cells (TICs) of osteosarcoma are useful to suppress tumor growth and metastasis, and prolong survival. Antisense oligonucleotides to miR-133a are synergistic in combination with standard chemotherapy such as cisplatin in the treatment of osteosarcoma.

1 - 21 . (canceled) 
     
     
         22 . A method of screening for osteosarcoma, comprising:
 performing on a tissue sample from a subject an assay specifically capable of detecting at least one microRNA (miRNA) selected from the group consisting of miR-1, miR-10b, and miR-133a, wherein detection by the assay of the presence in the sample of the at least one miRNA indicates the subject is at risk of having osteosarcoma.   
     
     
         23 . The method of  claim 22 , wherein the tissue is blood. 
     
     
         24 . The method of  claim 22 , wherein the tissue is serum. 
     
     
         25 - 27 . (canceled) 
     
     
         28 . The method of  claim 22 , wherein the miRNA is miR-1. 
     
     
         29 . The method of  claim 22 , wherein the miRNA is miR-10b. 
     
     
         30 . The method of  claim 22 , wherein the miRNA is miR-133a. 
     
     
         31 . The method of  claim 22 , wherein the assay comprises RT-PCR using oligonucleotide primers suitable for reverse transcribing and amplifying at least one miRNA selected from the group consisting of miR-1, miR-10b, and miR-133a. 
     
     
         32 . The method of  claim 31 , wherein the miRNA is miR-1. 
     
     
         33 . The method of  claim 31 , wherein the miRNA is miR-10b. 
     
     
         34 . The method of  claim 31 , wherein the miRNA is miR-133a. 
     
     
         35 . The method of  claim 22 , further comprising the step of verifying the presence of osteosarcoma in the subject when the subject is determined to be at risk of having osteosarcoma. 
     
     
         36 . The method of  claim 35 , wherein verifying the presence of osteosarcoma in the subject comprises performing on the subject a diagnostic procedure selected from the group consisting of skeletal survey or specific bone imaging analysis using X-rays or other suitable bone imaging technique, magnetic resonance imaging (MRI), computed tomography (CT), biopsy, and any combination thereof. 
     
     
         37 . The method of  claim 35 , wherein the miRNA is miR-1. 
     
     
         38 . The method of  claim 35 , wherein the miRNA is miR-10b. 
     
     
         39 . The method of  claim 35 , wherein the miRNA is miR-133a. 
     
     
         40 . The method of  claim 35 , further comprising the step of treating the subject for osteosarcoma. 
     
     
         41 . The method of  claim 22 , further comprising the step of treating the subject for osteosarcoma.