Micrornaome

A pharmaceutical composition comprising an isolated DNA or RNA polynucleotide comprising a sequence of approximately 17-250 nucleotides of an miRNA selected from any one of SEQ ID NOS:

• 1-5, 7-10, 12, 15-17, 19-23, 26-27, 29, 31-34, 36-37, 39-40, 42, 49, 48-49, 51-52, 54-55, 57, 59, 62-63, 65, 76-77, 80, 85-86, 94, 96, 101, 112, 115, 337-469 and 1386-1518 or the complement of a sequence selected from any one of SEQ ID NOS:
• 1-5, 7-10, 12, 15-17, 19-23, 26-27, 29, 31-34, 36-37, 39-40, 42, 49, 48-49, 51-52, 54-55, 57, 59, 62-63, 65, 76-77, 80, 85-86, 94, 96, 101, 112, 115, 337-469 and 1386-1518, and a pharmaceutically acceptable carrier.

An isolated cell line comprising homozygous RNaseIII enzyme Dicer-deficient human cells, wherein the cells display a hypomorphic phenotype, and wherein the helicase domain of RNaseIII enzyme Dicer is disrupted.

A pair of isogenic cells, wherein a first cell of said pair of cells is a homozygous RNaseIII enzyme Dicer-deficient human cell, wherein the first cell displays a hypomorphic phenotype, and wherein the helicase domain of RNaseIII enzyme Dicer of the first cell is disrupted;

• and wherein the second cell is homozygous RNaseIII enzyme Dicer-proficient.

A method of diagnosing a cancer in a patient comprising:

• detecting the presence of an miRNA or miRNA precursor selected from the group consisting of any one of SEQ ID NOS:
• 337-469 and 1386-1518 in a body fluid or tumor specimen from the patient, wherein the miRNA or miRNA precursor is expressed in tumor tissue or cell lines but not in normal tissue;
• identifying a cancer in the patient when the miRNA or miRNA precursor is detected in the body fluid or tumor specimen from the patient.

A method of diagnosing a cancer in a patient comprising:

• assaying to detect presence or absence of an miRNA or its precursor selected from the group consisting of any one of SEQ ID NOS:
• 337-469 and 1386-1518 in a body fluid or tumor specimen from the patient, wherein the miRNA or its precursor is expressed in normal tissue but not in tumor tissue or cell lines;
• identifying a cancer in the patient when absence of the miRNA is detected in the body fluid or tumor specimen.

A method of diagnosing a colorectal cancer in a subject in need thereof, the method comprising:

• detecting in a test sample from the subject and in a normal sample a miRNA selected from any one of SEQ ID NOS:
• 1-5, 7-10, 12, 15-17, 19-23, 26-27, 29, 31-34, 36-37, 39-40, 42, 49, 48-49, 51-52, 54-55, 57, 59, 62-63, 65, 76-77, 80, 85-86, 94, 96, 101, 112, 115, 337-469 and 1386-1518;
• comparing the amount detected in the test sample to that detected in the normal sample, wherein a ratio of less than 0.7 or greater than 1.4 indicates a colorectal cancer in said subject.

A method of treating a colorectal cancer in a subject in need thereof, comprising the steps of:

• administering to the subject a composition comprising (a) an miRNA selected from any one of SEQ ID NOS:
• 1-5, 7-10, 12, 15-17, 19-23, 26-27, 29, 31-34, 36-37, 39-40, 42, 49, 48-49, 51-52, 54-55, 57, 59, 62-63, 65, 76-77, 80, 85-86, 94, 96, 101, 112, and 115 or (b) an miRNA* of an miRNA selected from any one of SEQ ID NOS 1-5, 7-10, 12, 15-17, 19-23, 26-27, 29, 31-34, 36-37, 39-40, 42, 49, 48-49, 51-52, 54-55, 57, 59, 62-63, 65, 76-77, 80, 85-86, 94, 96, 101, 112, and 115;
• whereby growth of the tumor is arrested, slowed, or reversed.

A method of experimentally validating a candidate miRNA, comprising the steps of:

• determining generation of the candidate miRNA in an isogenic pair of cells which differ in the dicer locus, wherein a first of the pair of cells is hypomorphic for RNaseIII enzyme Dicer activity and a second of the pair of cells has wild-type RNaseIII enzyme Dicer activity;
• comparing the determined generation of the candidate miRNA in the first of the pair of cells to the determined generation of the candidate miRNA in the second of the pair of cells, wherein a statistically significant reduction of generation of the candidate miRNA in the first relative to the second provides experimental validation that the candidate miRNA is a physiologically relevant miRNA.

A method of screening for test agents which affect miRNA generation, comprising the steps of:

• contacting a test agent with a cancer cell;
• determining generation of an miRNA in the cancer cell contacted with the test agent, wherein the miRNA is one whose generation is increased or decreased in cancer cells relative to normal cells;
• comparing the determined generation of the miRNA in the cells contacted with the test agent to generation of the miRNA in cells not contacted with the test agent, wherein a test agent is identified as a potential therapeutic agent if it increases the amount of an miRNA whose generation is decreased in cancer cells or if it decreases the amount of an miRNA whose generation is increased in cancer cells.