miR-200 Family Induces Mesenchymal-to-Epithelial Transition (MET) in Ovarian Cancer Cells

Abstract

The present invention provides a method of treating an ovarian cancer, the method comprising delivering one or more miR-200 family members to a mammalian subject in need thereof in an amount effective to treat the ovarian cancer. Also provided are methods of preventing metastasis of an ovarian cancer, the method comprising delivering one or more miR-200 family members to a mammalian subject in need thereof in an amount effective to prevent metastasis. Further provided are methods of sensitizing an ovarian cancer to a cytotoxic therapy, the method comprising delivering one or more miR-200 family members to a mammalian subject in need thereof in an amount effective to sensitize the ovarian cancer to the cytotoxic therapy. The invention also contemplates methods of reducing epithelial-to-mesenchymal transition (EMT) in an ovarian cancer or cancer cell as well as methods of inducing mesenchymal-to-epithelial transition (MET).

1 . A method of treating an ovarian cancer, preventing metastasis of an ovarian cancer and/or sensitizing an ovarian cancer to a cytotoxic therapy, the method comprising delivering one or more miR-200 family members to a mammalian subject in need thereof in an amount effective to treat the ovarian cancer, to prevent metastasis of the ovarian cancer and/or to sensitize the ovarian cancer to cytotoxic therapy. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . A method of reducing epithelial-to-mesenchymal transition in an ovarian cancer, the method comprising delivering one or more miR-200 family members to a mammalian subject in need thereof in an amount effective to reduce epithelial-to-mesenchymal transition in the ovarian cancer. 
     
     
         5 . A method of inducing mesenchymal-to-epithelial transition in an ovarian cancer, the method comprising delivering one or more miR-200 family members to a mammalian subject in need thereof in an amount effective to induce mesenchymal-to-epithelial transition in the ovarian cancer. 
     
     
         6 . The method of  claim 1 , wherein the method further comprises detecting a level of one or more miR-200 family members in ovarian cancer tissue from the subject prior to administering the one or more miR-200 family members to the subject. 
     
     
         7 . The method of  claim 1 , wherein the method further comprises detecting a level of cells having a mesenchymal phenotype in ovarian cancer tissue from the subject prior to administering the one or more miR-200 family members to the subject. 
     
     
         8 . The method of  claim 1 , wherein the method further comprises administering a cytotoxic therapy prior to, concurrently with and/or after administration of the one or more miR-200 family members. 
     
     
         9 . The method of  claim 8 , wherein the cytotoxic therapy comprises a chemotherapy agent. 
     
     
         10 . The method of  claim 8 , wherein the cytotoxic therapy comprises radiation therapy. 
     
     
         11 . The method of  claim 1 , wherein the one or more miR-200 family members are transiently delivered by lipofection, a nanoparticle delivery system, or a nanogel delivery system. 
     
     
         12 . The method of  claim 11 , wherein the method comprises administration of a nanogel delivering the one or more miR-200 family members to the subject, wherein the nanogel comprises a crosslinked polymer particle comprising the active agent non-covalently associated with the nanogel. 
     
     
         13 . The method of  claim 12 , wherein the crosslinked polymer particle comprises poly(N-isopropylmethacrylamide) and N,N′-methylenebis(acrylamide). 
     
     
         14 . The method of  claim 12 , wherein the nanogel further comprises a cross-linked polymer shell comprising a functionalization agent, wherein the crosslinked polymer shell is disposed substantially around the crosslinked polymer particle. 
     
     
         15 . The method of  claim 14 , wherein the crosslinked polymer shell comprises poly(N-isopropylmethacrylamide), N,N′-methylenebis(acrylamide), and aminopropylmethacrylamide. 
     
     
         16 . The method of  claim 1 , wherein the one or more miR-200 family members are miR-141, miR-200a, miR-200b, miR-200c, miR-205 and/or miR-429. 
     
     
         17 . The method of  claim 1 , wherein the one or more miR-200 family members consists of miR-429. 
     
     
         18 . The method of  claim 1 , wherein a mature miR-429 is administered to the subject. 
     
     
         19 . The method of  claim 1 , wherein one or more human miR-200 family members are delivered. 
     
     
         20 . The method of  claim 1 , wherein the subject is a human subject. 
     
     
         21 - 23 . (canceled)