MiRNAs Useful to Reduce Lung Cancer Tumorigenesis and Chemotherapy Resistance and Related Compositions and Methods
AssigneeOhio State Innovation Foundation
InventorsCarlo M. Croce, Michela Garofalo
Life of this patent
Estimating the term…
Abstract
Disclosed are compositions, such as nucleic acids, vectors, cells, animal models and the like, useful to reduce tumor growth, cancer cell migration and various other cancer pathologies associated with EGFR (epidermal growth factor receptor) and MET (the receptor tyrosine kinase for hepatocyte growth factors) dyregulation, particularly in non-small cell lung carcinoma.
Claims63
A composition comprising a nucleic acid selected from the group consisting of:
- isolated nucleotides 154 through 160 of the miR-221/222 binding site of APAF-1 (5′-ATGTAGC-3′);
- isolated nucleotides 288 through 294 of the miR-30b binding site of BIM (5′-TGTTTACA-3′);
- isolated nucleotides complementary to the 27 through 33 of the miR-103 binding site of PKC-ε (complement:
- 3′-ACGACG-5′);
- isolated nucleotides complementary to nucleotides 1517 through 1523 of the miR-103 binding site of PKC-ε (complement:
- 3′-ACGACG);
- isolated nucleotides complementary to nucleotides 1564 through 1570 of the miR-103 binding site of PKC-ε (complement:
- 3′-ACGACG-5′);
- isolated nucleotides complementary to nucleotides 656 through 662 of the miR-203 binding site of SRC (complement:
- 3′-UAAAGU-5′);
- isolated nucleotides complementary to nucleotides 1116 through 1122 of the miR-203 binding site of SRC (complement:
- 3′-UAAAGU-5′);
- isolated nucleotides complementary to nucleotides 1595 through 1601 of the miR-203 binding site of SRC (complement:
- 3′-UAAAGU-5′);
- and isolated nucleotides complementary to nucleotides 1706 through 1712 of the miR-203 binding site of SRC (complement:
- 3′-UAAAGU-5′).
An isolated nucleic acid comprising a nucleic acid selected from the group consisting of:
- 5′-ATGTAGC-3′;
- 5′-TGTTTACA-3′;
- 3′-ACGACG-5′;
- and 3′-UAAAGU-5′.
A composition of matter comprising at least one miR selected from the group consisting of:
- miR-103;
- miR-203;
- anti-miR-30;
- and anti-miR-221.
A method to downregulate DICER in a mammalian cell, comprising increasing miR-103 and/or miR-203 availability in a mammalian cell, and downregulating DICER in the mammalian cell.
A method to decrease migration in a mammalian cancer cell, comprising increasing miR-103 and/or miR-203 availability in a mammalian cancer cell, and decreasing migration of the mammalian cancer cell.
A method to decrease EGFR chemotherapy resistance of a mammalian cancer cell, comprising increasing miR-103 and/or miR-203 availability in a mammalian cancer cell, and decreasing EGFR chemotherapy resistance of the mammalian cancer cell.
A method to decrease gefitinib resistance of, or increase gefitinib sensitivity in, a mammalian cancer cell, comprising increasing miR-103 and/or miR-203 availability in a mammalian cancer cell, and decreasing gefitinib resistance of, or increasing gefitinib sensitivity in, the mammalian cancer cell.
A method to decrease expression of mesenchymal markers in a mammalian cancer cell, comprising increasing miR-103 and/or miR-203 availability in a mammalian cancer cell, and decreasing expression of mesenchymal markers in the mammalian cancer cell.
A method to increase expression of E-cadherin expression in a mammalian cancer cell, comprising increasing miR-103 and/or miR-203 availability in a mammalian cancer cell, and increasing expression of E-cadherin expression in the mammalian cancer cell.
A method to induce mesenchymal-epithelial transition in a mammalian cancer cell, comprising increasing miR-103 and/or miR-203 availability in a mammalian cancer cell, and inducing mesenchymal-epithelial transition in the mammalian cancer cell.
A method to induce programmed cell death in a mammalian cancer cell, comprising increasing miR-103 and/or miR-203 availability in a mammalian cancer cell, and inducing programmed cell death of the mammalian cancer cell.
A method to downregulate AKT/ERK in a mammalian cancer cell, comprising increasing miR-103 and/or miR-203 availability in a mammalian cancer cell, and downregulating AKT/ERK in the mammalian cancer cell.
(canceled)
A method to inhibit tumor growth in a mammal in need of tumor growth inhibition, comprising administering a tumor growth-inhibiting amount of at least one nucleic acid selected from the group consisting of:
- isolated nucleotides 154 through 160 of the miR-221/222 binding site of APAF-1 (5′-ATGTAGC-3′);
- isolated nucleotides 288 through 294 of the miR-30b binding site of BIM (5′-TGTTTACA-3′);
- isolated nucleotides complementary to nucleotides 27 through 33 of the miR-103 binding site of PKC-ε (complement:
- 3′-ACGACG-5′);
- isolated nucleotides complementary to nucleotides 1517 through 1523 of the miR-103 binding site of PKC-ε (complement:
- 3′-ACGACG);
- isolated nucleotides complementary to nucleotides 1564 through 1570 of the miR-103 binding site of PKC-ε (complement:
- 3′-ACGACG-5′);
- isolated nucleotides complementary to nucleotides 656 through 662 of the miR-203 binding site of SRC (complement:
- 3′-UAAAGU-5′);
- isolated nucleotides complementary to nucleotides 1116 through 1122 of the miR-203 binding site of SRC (complement:
- 3′-UAAAGU-5′);
- isolated nucleotides complementary to nucleotides 1595 through 1601 of the miR-203 binding site of SRC (complement:
- 3′-UAAAGU-5′);
- and isolated nucleotides complementary to nucleotides 1706 through 1712 of the miR-203 binding site of SRC (complement:
- 3′-UAAAGU-5′).
A method to inhibit tumor growth in a mammal in need of tumor growth inhibition, comprising administering a tumor growth-inhibiting amount of a nucleic acid selected from the group consisting of:
- 5′-ATGTAGC-3′;
- 5′-TGTTTACA-3′;
- 3′-ACGACG-5′;
- and 3′-UAAAGU-5′.
A method to inhibit tumor growth in a mammal in need of tumor growth inhibition, comprising administering a tumor growth-inhibiting amount of at least one miR selected from the group consisting of:
- miR-103;
- miR-203;
- anti-miR-30;
- and anti-miR-221.
40-42. (canceled)
Dependencies are inferred from the claim text.