# US 2014/0155459 A1 · Compositions and Methods of Using Micro RNAs > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0155459 A1 - Document ID: US20140155459A1 - Status: Published application - Kind: A1 - Application number: 14/080,412 - Filed: 2013-11-14 - Published: 2014-06-05 - Earliest claimed: 2012-11-15 - Assignees: Yale University - Applicants: Yale University - Inventors: Hyung J. Chun; Jongmin Kim - Web page: https://patentgrep.com/patent/US20140155459A1 ## CPC - C12N 15/1136: {against growth factors, growth regulators, cytokines, lymphokines or hormones} - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - G01N 33/6893: {related to diseases not provided for elsewhere} - C12Q 2600/112: Disease subtyping, staging or classification - C12Q 2600/178: miRNA, siRNA or ncRNA - G01N 2800/12: Pulmonary diseases - G01N 2800/321: Arterial hypertension - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract The present invention provides compositions and methods of using microRNAs to treat pulmonary arterial hypertension. In one aspect, methods are disclosed that are useful for identifying a subject in need of therapeutic intervention to reduce or improve a symptom of pulmonary arterial hypertension, reducing proliferation of pulmonary vascular cells in a subject, or treating pulmonary arterial hypertension in a subject. In another aspect, compositions include an inhibitor of fibroblast growth factor 2 (FGF2) expression comprising at least one of: a mature sequence of miR-424 or miR-503; a pri-miRNA of miR-424 or miR-503; a pre-miRNA of miR-424 or miR-503; and the complement thereof. Pharmaceutical compositions for reducing proliferation of pulmonary vascular cells in a subject in need thereof and biomarker panels are also disclosed. ## Claims ### Claim 1 A composition comprising an inhibitor of fibroblast growth factor 2 (FGF2) expression comprising at least one of: a mature sequence of miR-424 or miR-503; a pri-miRNA of miR-424 or miR-503; a pre-miRNA of miR-424 or miR-503; and the complement thereof. ### Claim 2 (depends on 1) The composition of claim 1, wherein the mature sequence comprises a polynucleotide selected from the group consisting of: a nucleotide sequence as shown in SEQ ID NO: 9 or SEQ ID NO: 10; a nucleotide sequence consisting of 30 to 120 nucleotides which has an identity of at least 85% to the nucleotide sequence as shown in SEQ ID NO: 9 or SEQ ID NO: 10; or the complement thereof. ### Claim 3 (depends on 1) The composition of claim 1, wherein the inhibitor is expressed by a recombinant expression vector. ### Claim 4 (depends on 1) A pharmaceutical composition for reducing proliferation of pulmonary vascular cells in a subject in need thereof comprising the composition of claim 1 and a pharmaceutically acceptable carrier. ### Claim 5 A method of identifying a subject in need of therapeutic intervention to reduce or improve a symptom of pulmonary arterial hypertension comprising, detecting an alteration in the level of a biomarker selected from the group consisting of fibroblast growth factor 2 (FGF2), apelin (APLN), miR-424, and miR-503 in a sample from the subject relative to a reference, thereby identifying the subject as in need of therapeutic intervention to reduce or improve the symptom of pulmonary arterial hypertension. ### Claim 6 (depends on 5) The method of claim 5, wherein the level of FGF2 is increased relative to the reference. ### Claim 7 (depends on 5) The method of claim 5, wherein the level of APLN is decreased relative to the reference. ### Claim 8 (depends on 5) The method of claim 5, wherein the level of miR-424 is decreased relative to the reference. ### Claim 9 (depends on 5) The method of claim 5, wherein the level of miR-503 is decreased relative to the reference. ### Claim 10 (depends on 5) The method of claim 5, further comprising measuring a biomarker selected from the group consisting of fibroblast growth factor receptor 1 (FGFR1), apelin receptor (APLNR), argonaute 2 (Ago2), miR-15a, miR-16, miR-195 and miR-497. ### Claim 11 (depends on 5) The method of claim 5, wherein the step of detecting the alteration comprises detecting increased levels of fibroblast growth factor 2 (FGF2) and decreased levels of apelin (APLN), miR-424 and miR-503 in the sample. ### Claim 12 A method of reducing proliferation of pulmonary vascular cells in a subject in need thereof comprising administering to the pulmonary vascular cells of the subject a composition comprising an inhibitor of fibroblast growth factor 2 (FGF2) expression comprising at least one of: a mature sequence of miR-424 or miR-503; a pri-miRNA of miR-424 or miR-503; a pre-miRNA of miR-424 or miR-503; and the complement thereof, wherein the proliferation of pulmonary vascular cells is reduced in the subject following administration of the composition. ### Claim 13 (depends on 12) The method of claim 12, wherein the mature sequence comprises a polynucleotide selected from the group consisting of: a nucleotide sequence as shown in SEQ ID NO: 9 or SEQ ID NO: 10; a nucleotide sequence consisting of 30 to 120 nucleotides which has an identity of at least 85% to the nucleotide sequence as shown in SEQ ID NO: 9 or SEQ ID NO: 10; or the complement thereof, wherein the pulmonary arterial hypertension is reduced in the subject following administration of the composition. ### Claim 14 A method of treating pulmonary arterial hypertension in a subject in need thereof comprising administering to the pulmonary vascular cells of the subject an inhibitor of fibroblast growth factor 2 (FGF2) expression comprising at least one of: a mature sequence of miR-424 or miR-503; a pri-miRNA of miR-424 or miR-503; a pre-miRNA of miR-424 or miR-503; and the complement thereof, and wherein the pulmonary arterial hypertension is reduced in the subject following administration of the inhibitor. ### Claim 15 (depends on 14) The method of claim 14, wherein the mature sequence comprises a polynucleotide selected from the group consisting of: a nucleotide sequence as shown in SEQ ID NO: 9 or SEQ ID NO: 10; a nucleotide sequence consisting of 30 to 120 nucleotides which has an identity of at least 85% to the nucleotide sequence as shown in SEQ ID NO: 9 or SEQ ID NO: 10; or the complement thereof. ### Claim 16 (depends on 14) The method of claim 14, wherein the step of administering the inhibitor further comprises administering a recombinant expression vector comprising the inhibitor. ### Claim 17 A biomarker panel comprising fibroblast growth factor 2 (FGF2), apelin (APLN), miR-424 and miR-503 or capture molecules that specifically bind the biomarkers. ### Claim 18 (depends on 17) The biomarker panel of claim 17, further comprising fibroblast growth factor receptor 1 (FGFR1), apelin receptor (APLNR), argonaute 2 (Ago2), miR-15a, miR-16, miR-195 and miR-497 or capture molecules that specifically bind the biomarkers.