Micrornas and uses thereof

Abstract

Described herein are novel polynucleotides associated with prostate and lung cancer. The polynucleotides are miRNAs and miRNA precursors. Related methods and compositions that can be used for diagnosis, prognosis, and treatment of those medical conditions are disclosed. Also described herein are methods that can be used to identify modulators of prostate and lung cancer.

1 . An isolated nucleic acid comprising a sequence selected from the group consisting of:
 (a) the sequence of a hairpin referred to in Table 1;   (b) the sequence of sequence identifiers 6757248-6894882 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572;   (c) the sequence of sequence identifiers 1-6318 or 18728-18960 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094;   (d) the sequence of a miRNA referred to in Table 1;   (e) the sequence of sequence identifiers 1.117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572;   (f) the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094;   (g) the sequence of a target gene binding site referred to in Table 4;   (h) the sequence of sequence identifiers 117751-6757247 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572;   (i) complement of (a)-(h);   (j) nucleotide sequence comprising at least 12 contiguous nucleotides at least 60% identical to (a)-(h);   wherein the nucleic acid is from 5-250 nucleotides in length.   
     
     
         2 . A probe comprising the nucleic acid of  claim 1 . 
     
     
         3 . The probe of  claim 2  wherein the nucleic acid comprises at least 8-22 contiguous nucleotides complementary to a miRNA referred to in Table 2 as differentially expressed in prostate cancer or lung cancer. 
     
     
         4 . A plurality of probes of  claim 3 . 
     
     
         5 . The plurality of probes of  claim 4  comprising at least one probe complementary to each miRNA referred to in Table 2 as differentially expressed in prostate cancer. 
     
     
         6 . The plurality of probes of  claim 4  comprising at least one probe complementary to each miRNA referred to in Table 2 as differentially expressed in lung cancer. 
     
     
         7 . A composition comprising the plurality of probes of  claim 3 . 
     
     
         8 . A biochip comprising a solid substrate, said substrate comprising a plurality of probes of  claim 3 , wherein each probe is attached to the substrate at a spatially defined address. 
     
     
         9 . The biochip of  claim 8  wherein the probes are complementary to a miRNA referred to in Table 2 as differentially expressed in prostate cancer. 
     
     
         10 . The biochip of  claim 8  wherein the probes are complementary to a miRNA referred to in Table 2 as differentially expressed in lung cancer. 
     
     
         11 . A method for detecting differential expression of a miRNA comprising:
 (a) providing a biological sample; and   (b) measuring the level of a nucleic acid at least 70% identical to (i) a sequence of a miRNA referred to in Table 1, (ii) the sequence of sequence identifiers 1-117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, (iii) the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, or (iv) a variant of (i)-(iii),   wherein a difference in the level of the nucleic acid compared to a control is indicative of differential expression.   
     
     
         12 . A method for identifying a compound that modulates expression of a miRNA:
 (a) providing a cell that is capable of expressing a nucleic acid at least 70% identical to (i) a sequence of a miRNA referred to in Table 1, (ii) the sequence of sequence identifiers 1-117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, (iii) the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, or (iv) a variant of (i)-(iii);   (b) contacting the cell with a candidate modulator; and   (c) measuring the level of expression of the nucleic acid,   wherein a difference in the level of the nucleic acid compared to a control identifies the compound as a modulator of expression of the miRNA.   
     
     
         13 . A method of inhibiting expression of a target gene in a cell comprising introducing a nucleic acid into the cell in an amount sufficient to inhibit expression of the target gene, wherein the target gene comprises a (i) binding site substantially identical to a binding site referred to in Table 4, (ii) sequence of sequence identifiers 117751-6757247 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, or (iii) a variant of (i) or (ii); and wherein the nucleic acid comprises a sequence (a) of SEQ ID NOS: 1-760616, (b) sequence of sequence identifiers 1-117750 and 6757248-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, (c) a sequence set forth on the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, or (d) a variant of (a)-(c). 
     
     
         14 . The method of  claim 12  wherein expression is inhibited in vitro or in vivo. 
     
     
         15 . A method of increasing expression of a target gene in a cell comprising introducing a nucleic acid into the cell in an amount sufficient to increase expression of the target gene, wherein the target gene comprises a (i) binding site substantially identical to a binding site referred to in Table 4, (ii) sequence of sequence identifiers 117751-6757247 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, or (iii) a variant of (i) or (ii); wherein the nucleic acid comprises a sequence substantially complementary to a sequence (a) of SEQ ID NOS: 1-760.616, (b) set forth on the Sequence Listing of U.S. patent application Ser. No. 10/709,572, (c) a sequence set forth on the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, or (d) a variant of (a)-(c). 
     
     
         16 . The method of  claim 15  wherein expression is inhibited in vitro or in vivo. 
     
     
         17 . A method of treating a patient with a disorder set forth on Table 6 comprising administering to a patient in need thereof a composition comprising the nucleic acid of  claim 1 .