Diagnosis And Treatment Of Cancers With MicroRNA Located In Or Near Cancer-Associated Chromosomal Features

Abstract

MicroRNA genes are highly associated with chromosomal features involved in the etiology of different cancers. The perturbations in the genomic structure or chromosomal architecture of a cell caused by these cancer-associated chromosomal features can affect the expression of the miR gene(s) located in close proximity to that chromosomal feature. Evaluation of miR gene expression can therefore be used to indicate the presence of a cancer-causing chromosomal lesion in a subject. As the change in miR gene expression level caused by a cancer-associated chromosomal feature may also contribute to cancerigenesis, a given cancer can be treated by restoring the level of miR gene expression to normal. microRNA expression profiling can be used to diagnose cancer and predict whether a particular cancer is associated with an adverse prognosis. The identification of specific mutations associated with genomic regions that harbor miR genes in CLL patients provides a means for diagnosing CLL and possibly other cancers.

What is claimed is: 
     
         1 . A method for increasing expression of a miR-34 gene product in cancer cells, wherein the cancer cells are pancreatic cancer cells, lung cancer cells, breast cancer cells, gastric cancer cells, colorectal cancer cells or prostate cancer cells, the method comprising delivering to the cancer cells a nucleic acid comprising a miR-34 gene product, or a nucleic acid encoding a miR-34 gene product, thereby increasing the expression of the miR-34 gene product in the cancer cells. 
     
     
         2 . The method of  claim 1 , comprising delivering a nucleic acid comprising a miR-34 gene product to the cancer cells. 
     
     
         3 . The method of  claim 2 , wherein the miR-34 gene product contains a contiguous nucleotide sequence that is at least 95% identical to SEQ ID NO:79 or nucleotides 22-43 of SEQ ID NO:79. 
     
     
         4 . The method of  claim 3 , wherein the miR-34 gene product contains a contiguous nucleotide sequence that is 100% identical to SEQ ID NO:79 or nucleotides 22-43 of SEQ ID NO:79. 
     
     
         5 . The method of  claim 2 , wherein the nucleic acid comprising a miR-34 gene product is a single-stranded RNA. 
     
     
         6 . The method of  claim 2 , wherein the nucleic acid comprising a miR-34 gene product contains one or more modifications to the nucleic acid backbone, a sugar moiety, a base moiety or a combination thereof. 
     
     
         7 . The method of  claim 1 , comprising delivering a nucleic acid encoding a miR-34 gene product to the cancer cells. 
     
     
         8 . The method of  claim 7 , wherein the nucleic acid encodes a miR-34 gene product containing a contiguous nucleotide sequence that is 100% identical to SEQ ID NO:79 or nucleotides 22-43 of SEQ ID NO:79. 
     
     
         9 . The method of  claim 7 , wherein the nucleic acid encoding a miR-34 gene product is a double-stranded DNA. 
     
     
         10 . The method of  claim 9 , wherein the double-stranded DNA is in a plasmid vector. 
     
     
         11 . The method of  claim 9 , wherein the double-stranded DNA is in a viral vector. 
     
     
         12 . The method of  claim 11 , wherein the viral vector is an adenovirus vector, an adeno-associated virus vector or a cytomegalovirus vector. 
     
     
         13 . The method of  claim 1 , wherein the cancer cells are in a tumor. 
     
     
         14 . The method of  claim 1 , wherein the cancer cells are pancreatic cancer cells. 
     
     
         15 . The method of  claim 1 , wherein the cancer cells are lung cancer cells. 
     
     
         16 . The method of  claim 1 , wherein the cancer cells are breast cancer cells. 
     
     
         17 . The method of  claim 1 , wherein the cancer cells are gastric cancer cells. 
     
     
         18 . The method of  claim 1 , wherein the cancer cells are colorectal cancer cells. 
     
     
         19 . The method of  claim 1 , wherein the cancer cells are prostate cancer cells. 
     
     
         20 . The method of  claim 1 , wherein the nucleic acid comprising a miR-34 gene product, or a nucleic acid encoding a miR-34 gene product, is delivered to the cancer cells in a pharmaceutical composition comprising a pharmaceutically-acceptable carrier.