MicroRna-Based Methods and Compositions for the Diagnosis, Prognosis and Treatment of Solid Cancers
AssigneeThe Ohio State University
InventorsCarlo M. Croce, George A. Calin, Stefano Volinia
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Abstract
The present invention provides novel methods and compositions for the diagnosis and treatment of solid cancers. The invention also provide methods of identifying inhibitors of tumorigenesis.
Claims33
A method of diagnosing whether a subject has, or is at risk for developing, a solid cancer, comprising measuring the level of at least one miR gene product in a test sample from the subject, wherein an alteration in the level of the miR gene product in the test sample, relative to the level of a corresponding miR gene product in a control sample, is indicative of the subject either having, or being at risk for developing, a solid cancer.
A method of diagnosing whether a subject has, or is at risk for developing, a solid cancer, comprising:
- (1) reverse transcribing RNA from a test sample obtained from the subject to provide a set of target oligodeoxynucleotides;
- (2) hybridizing the target oligodeoxynucleotides to a microarray comprising miRNA-specific probe oligonucleotides to provide a hybridization profile for the test sample;
- and
- (3) comparing the test sample hybridization profile to a hybridization profile generated from a control sample,
- wherein an alteration in the signal of at least one miRNA is indicative of the subject either having, or being at risk for developing, a solid cancer.
A method of inhibiting tumorigenesis in a subject who has, or is suspected of having, a solid cancer in which at least one miR gene product is down-regulated or up-regulated in the cancer cells of the subject, relative to control cells, comprising:
- (1) when the at least one miR gene product is down-regulated in the cancer cells, administering to the subject an effective amount of at least one isolated miR gene product, or an isolated variant or biologically-active fragment thereof, provided that the miR gene product is not miR-15a or miR-16-1, such that tumorigenesis is inhibited in the subject;
- or
- (2) when the at least one miR gene product is up-regulated in the cancer cells, administering to the subject an effective amount of at least one compound for inhibiting expression of the at least one miR gene product, such that tumorigenesis is inhibited in the subject.
A method of inhibiting tumorigenesis in a subject who has a solid cancer, comprising:
- (1) determining the amount of at least one miR gene product in cancer cells from the subject, relative to control cells;
- and
- (2) altering the amount of miR gene product expressed in the cancer cells by:
- (i) administering to the subject an effective amount of at least one isolated miR gene product, or an isolated variant or biologically-active fragment thereof, provided that the miR gene product is not miR-15a or miR-16-1, if the amount of the miR gene product expressed in the cancer cells is less than the amount of the miR gene product expressed in control cells;
- or
- (ii) administering to the subject an effective amount of at least one compound for inhibiting expression of the at least one miR gene product, if the amount of the miR gene product expressed in the cancer cells is greater than the amount of the miR gene product expressed in control cells,
- such that tumorigenesis is inhibited in the subject.
A pharmaceutical composition for treating a solid cancer, comprising at least one isolated miR gene product, or an isolated variant or biologically-active fragment thereof, and a pharmaceutically-acceptable carrier.
A pharmaceutical composition for treating a solid cancer, comprising at least one miR expression-inhibition compound and a pharmaceutically-acceptable carrier.
A method of identifying an inhibitor of tumorigenesis, comprising providing a test agent to a cell and measuring the level of at least one miR gene product associated with decreased expression levels in solid cancers, wherein an increase in the level of the miR gene product in the cell, relative to a suitable control cell, is indicative of the test agent being an inhibitor of tumorigenesis.
The method of claim 29, wherein the miR gene product is selected from the group consisting of miR-145, miR-155, miR-218-2 and combinations thereof.
A method of identifying an inhibitor of tumorigenesis, comprising providing a test agent to a cell and measuring the level of at least one miR gene product associated with increased expression levels in solid cancers, wherein a decrease in the level of the miR gene product in the cell, relative to a suitable control cell, is indicative of the test agent being an inhibitor of tumorigenesis.
The method of claim 32, wherein the miR gene product is selected from the group consisting of miR-21, miR-17-5p, miR-191, miR-29b-2, miR-223, miR-128b, miR-199a-1, miR-24-1, miR-24-2, miR-146, miR-155, miR-181b-1, miR-20a, miR-107, miR-32, miR-92-2, miR-214, miR-30c, miR-25, miR-221, miR-106a and combinations thereof.
Dependencies are inferred from the claim text.