MicroRNA Signatures in Human Ovarian Cancer
AssigneeThe Ohio State University Research Foundation
InventorCarlo M. Croce
Life of this patent
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Abstract
The present invention provides novel methods and compositions for the diagnosis, prognosis and treatment of ovarian cancer. The invention also provides methods of identifying anti-cancer agents.
Claims55
A method of diagnosing whether a subject has, or
- is at risk for developing, ovarian cancer, comprising:
- measuring the level of at least one miR in a test sample from the subject, wherein at least one miR is selected from a miR profile comprising:
- miR-200a, miR-200b, miR-200c, miR-141, miR-199a, miR-140, miR-145 and miR-125b1, and
- wherein an alteration in the level of the miR in the test sample, relative to the level of a corresponding miR in a control sample, is indicative of the subject either having, or being at risk for developing, ovarian cancer .
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A method of diagnosing whether a subject has, or is at risk for developing, ovarian cancer, comprising:
- measuring the level of at least one miR in a test sample from the subject, wherein at least one miRNA is selected from the group consisting of miR-205, miR-21 and miR-182,
- wherein a difference in expression of one or more of the miRNA compared to a normal sample is indicative of endometrioid ovarian cancer.
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A method of inhibiting proliferation of an ovarian cancer cell comprising:
- i) introducing into the cell one or more agents which inhibit expression or activity of one or more miRs selected from a miR profile comprising:
- miR-200a, miR-200b, miR-200c, miR-141,
- ii) introducing into the cell one or more agents which enhances expression of one or more target genes of the miRs, or introducing into the cell a combination of the one or more agents of i) and ii), and
- maintaining the cells under conditions in which the one or more agents inhibits expression or activity of the miR, enhances expression or activity of one or more target genes of the miR, or results in a combination thereof, thereby inhibiting proliferation of the ovarian cancer cell.
A method for modulating levels of one or more of miR-21, miR-203, miR-146, miR-205, miR-30-5p and miR-30c in an ovarian cancer cell compared with normal tissues, comprising administering an effective amount of a demethylation agent.
A method for altering expression of one or more of miRs in a miR profile comprising:
- miR-21, miR-203, miR-146, miR-205, miR-30-5p and miR-30c in a subject diagnoses with ovarian cancer, comprising controlling the DNA hypomethylation mechanism responsible for overexpression thereof.
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A method of treating ovarian cancer in a subject who has a ovarian cancer in which at least one miR 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 is down-regulated in the cancer cells, administering to the subject an effective amount of at least one isolated miR, such that proliferation of cancer cells in the subject is inhibited;
- or
- (2) when the at least one miR 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, such that proliferation of cancer cells in the subject is inhibited;
- wherein the at least one isolated miR in step (1) is selected miR-199a, miR-140, miR-145 and miR-125b1, and combinations thereof;
- and/or
- wherein the at least one miR in step (2) is selected from the group consisting of miR-200a, miR-200b, miR-200c and miR-141, and combinations thereof.
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A method of treating ovarian cancer in a subject, comprising:
- (1) determining the amount of at least one miR in ovarian cancer cells, relative to control cells;
- and
- (2) altering the amount of the at least one miR expressed in the ovarian cancer cells by:
- i) administering to the subject an effective amount of at least one isolated miR, if the amount of the miR expressed in the cancer cells is less than the amount of the miR 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, if the amount of the miR expressed in the cancer cells is greater than the amount of the miR expressed in control cells, such that proliferation of cancer cells in the subject is inhibited;
- wherein the at least one isolated miR in steps (i) and/or (ii) is selected from the group consisting of miR-200a, miR-200b, miR-200c, miR-141, miR-199a, miR-140, miR-145 and miR-125b1, and combinations thereof.
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A pharmaceutical composition for treating ovarian cancer, comprising at least one isolated miR and a pharmaceutically-acceptable carrier, wherein the isolated miR is selected from the group consisting of miR-200a, miR-200b, miR-200c, miR-141, miR-199a, miR-140, miR-145 and miR-125b1, and combinations thereof.
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A method of identifying an anti-ovarian cancer agent, comprising providing a test agent to a cell and measuring the level of at least one miR associated with decreased expression levels in ovarian cancer cells, wherein an increase in the level of the miR in the cell, relative to a suitable control cell, is indicative of the test agent being an anti-ovarian cancer agent, wherein the miR is selected from the group consisting of miR-199a, miR-140, miR-145, miR-125b1, and combinations thereof.
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A method of identifying an anti-ovarian cancer agent, comprising providing a test agent to a cell and measuring the level of at least one miR associated with increased expression levels in ovarian cancer cells, wherein an decrease in the level of the miR in the cell, relative to a suitable control cell, is indicative of the test agent being an anti-ovarian cancer agent, wherein the miR is selected from the group consisting of miR-200a, miR-200b, miR-200c, miR-141, and combinations thereof.
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A kit for detecting ovarian cancer in an individual comprising
- one or more reagents for detecting one or more miRs selected from the group consisting of:
- miR-200a, miR-200b, miR-200c, miR-141, miR-199a, miR-140, miR-145 and miR-125b1, and combinations thereof,
- one or more target genes of one or more miRs selected from the group consisting of:
- miR-200a, miR-200b, miR-200c, miR-141, miR-199a, miR-140, miR-145 and miR-125b1, and combinations thereof shown in Table 3, in the individual compared to a control, or a combination thereof.
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Dependencies are inferred from the claim text.