US 8673872 B2 - Method Of Modulation Of Expression Of Epidermal Growth Factor Receptor(egfr) Involving Mirna - The Lens

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Abstract

The present invention relates to a method for modulating the expression of epidermal growth factor receptor (EGFR) and its downstream signalling effectors. In particular, the present invention relates to a method for modulating the expression of epidermal growth factor receptor (EGFR) or like molecule in a cell comprising contacting said cell with an agent capable of directly or indirectly interacting with the 3'-untranslated region (UTR) of the mRNA of said EGFR or like molecule, wherein the UTR is encoded by a sequence which comprises a sequence having at least about 70% identity with at least one sequence selected from the group consisting of the sequences set forth in SEQ ID NOs: 1-36.

Claims

A method for reducing the expression of epidermal growth factor receptor (EGFR) or a downstream effector molecule in a cell, comprising:
a) selecting an miRNA capable of interacting with the sequence UCUUCC in the 3′-untranslated region (UTR) of the mRNA of said EGFR or of a downstream effector molecule selected from the group consisting of Raf-1, CALM3, CAMK2D, PAK1, and ADCY9; and

b) contacting said cell with said miRNA under conditions whereby expression of EGFR in said cell is reduced.
The method of claim 1, wherein the 3′-UTR comprises a sequence which is encoded by a sequence having at least about 90% identity with at least one sequence selected from the group consisting of the sequences set forth in SEQ ID NOs:1-11.
The method of claim 1, wherein the 3′-UTR is encoded by a sequence contained within the sequence set forth in SEQ ID NO:1.
The method of claim 1, wherein said contacting comprises contacting said cell with an agent comprising a nucleic acid molecule encoding an miRNA precursor, wherein said precursor is processed in said cell to form said miRNA.
The method of claim 1, wherein the said miRNA is miR-7.
The method of claim 5, wherein the miR-7 is the sequence set forth in SEQ ID NO: 48.
The method of claim 1, wherein the miRNA comprises the sequence set fourth in SEQ ID NO: 52.
The method of claim 1, wherein the miRNA comprises a nucleic acid molecule having at least about 90% identity with the sequence set forth in SEQ ID NO: 48.
A method of inhibiting the growth or differentiation of a cell expressing EGFR or a downstream effector molecule, comprising:
a) selecting an miRNA capable of interacting with the sequence UCUUCC in the 3′-untranslated region (UTR) of the mRNA of said EGFR or of a downstream effector molecule selected from the group consisting of Raf-1, CALM3, CAMK2D, PAK1, and ADCY9; and

b) contacting said cell with said miRNA under conditions whereby growth or differentiation of said cell is inhibited.
The method of claim 9, wherein-said cell is a cancer cell.
The method of claim 10, wherein said cancer cell is selected from the group consisting of a brain cancer cell, a lung cancer cell, a breast cancer cell, a prostate cancer cell, and a colon cancer cell.
The method of claim 10, wherein said cancer cell is from a cancer cell line.
The method of claim 9, wherein the miRNA comprises the sequence set forth in SEQ ID NO: 52.
The method of claim 9, wherein the miRNA is miR-7.
The method of claim 9, wherein the miR-7 is the sequence set forth in SEQ ID NO: 48.
The method of claim 9, wherein the miRNA comprises a nucleic acid molecule having at least about 90% identity with the sequence set forth in SEQ ID NO: 48.