PubMed:25675535 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/25675535","sourcedb":"PubMed","sourceid":"25675535","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/25675535","text":"Silencing LRH-1 in colon cancer cell lines impairs proliferation and alters gene expression programs.\nColorectal cancers (CRCs) account for nearly 10% of all cancer deaths in industrialized countries. Recent evidence points to a central role for the nuclear receptor liver receptor homolog-1 (LRH-1) in intestinal tumorigenesis. Interaction of LRH-1 with the Wnt/β-catenin pathway, highly active in a critical subpopulation of CRC cells, underscores the importance of elucidating LRH-1's role in this disease. Reduction of LRH-1 diminishes tumor burden in murine models of CRC; however, it is not known whether LRH-1 is required for tumorigenesis, for proliferation, or for both. In this work, we address this question through shRNA-mediated silencing of LRH-1 in established CRC cell lines. LRH-1 mRNA knockdown results in significantly impaired proliferation in a cell line highly expressing the receptor and more modest impairment in a cell line with moderate LRH-1 expression. Cell-cycle analysis shows prolongation of G0/G1 with LRH-1 silencing, consistent with LRH-1 cell-cycle influences in other tissues. Cluster analysis of microarray gene expression demonstrates significant genome wide alterations with major effects in cell-cycle regulation, signal transduction, bile acid and cholesterol metabolism, and control of apoptosis. This study demonstrates a critical proproliferative role for LRH-1 in established colon cancer cell lines. LRH-1 exerts its effects via multiple signaling networks. Our results suggest that selected CRC patients could benefit from LRH-1 inhibitors.","tracks":[{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":1104,"end":1111},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":229,"end":236},"obj":"http://purl.obolibrary.org/obo/UBERON_0012131"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":267,"end":272},"obj":"http://purl.obolibrary.org/obo/UBERON_0002107"},{"id":"PD-UBERON-AE-B_T4","span":{"begin":19,"end":24},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"PD-UBERON-AE-B_T5","span":{"begin":1421,"end":1426},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"PD-UBERON-AE-B_T6","span":{"begin":303,"end":313},"obj":"http://purl.obolibrary.org/obo/UBERON_0000160"},{"id":"PD-UBERON-AE-B_T7","span":{"begin":1275,"end":1279},"obj":"http://purl.obolibrary.org/obo/UBERON_0001970"}],"attributes":[{"subj":"PD-UBERON-AE-B_T1","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T2","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T3","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T4","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T5","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T6","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T7","pred":"source","obj":"performance-test"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":113,"end":120},"obj":"HP_0002664"},{"id":"T2","span":{"begin":158,"end":164},"obj":"HP_0002664"},{"id":"T3","span":{"begin":540,"end":545},"obj":"HP_0002664"},{"id":"T4","span":{"begin":1421,"end":1433},"obj":"HP_0003003"},{"id":"T5","span":{"begin":1421,"end":1433},"obj":"HP_0100273"},{"id":"T6","span":{"begin":1427,"end":1433},"obj":"HP_0002664"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"},{"subj":"T4","pred":"source","obj":"PubmedHPO"},{"subj":"T5","pred":"source","obj":"PubmedHPO"},{"subj":"T6","pred":"source","obj":"PubmedHPO"}]},{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":101},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":102,"end":200},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":201,"end":328},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":329,"end":509},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":510,"end":679},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":680,"end":791},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":792,"end":980},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":981,"end":1112},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":1113,"end":1338},"obj":"Sentence"},{"id":"TextSentencer_T10","span":{"begin":1339,"end":1445},"obj":"Sentence"},{"id":"TextSentencer_T11","span":{"begin":1446,"end":1503},"obj":"Sentence"},{"id":"TextSentencer_T12","span":{"begin":1504,"end":1587},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":101},"obj":"Sentence"},{"id":"T2","span":{"begin":102,"end":200},"obj":"Sentence"},{"id":"T3","span":{"begin":201,"end":328},"obj":"Sentence"},{"id":"T4","span":{"begin":329,"end":509},"obj":"Sentence"},{"id":"T5","span":{"begin":510,"end":679},"obj":"Sentence"},{"id":"T6","span":{"begin":680,"end":791},"obj":"Sentence"},{"id":"T7","span":{"begin":792,"end":980},"obj":"Sentence"},{"id":"T8","span":{"begin":981,"end":1112},"obj":"Sentence"},{"id":"T9","span":{"begin":1113,"end":1338},"obj":"Sentence"},{"id":"T10","span":{"begin":1339,"end":1445},"obj":"Sentence"},{"id":"T11","span":{"begin":1446,"end":1503},"obj":"Sentence"},{"id":"T12","span":{"begin":1504,"end":1587},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"TextSentencer_T1","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T7","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T8","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T9","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T10","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T11","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T12","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"},{"subj":"T12","pred":"source","obj":"sentences"}]},{"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":19,"end":24},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":1421,"end":1426},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":229,"end":236},"obj":"http://purl.obolibrary.org/obo/UBERON_0012131"},{"id":"PD-UBERON-AE-B_T4","span":{"begin":267,"end":272},"obj":"http://purl.obolibrary.org/obo/UBERON_0002107"},{"id":"PD-UBERON-AE-B_T5","span":{"begin":303,"end":313},"obj":"http://purl.obolibrary.org/obo/UBERON_0000160"},{"id":"PD-UBERON-AE-B_T6","span":{"begin":1104,"end":1111},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T7","span":{"begin":1275,"end":1279},"obj":"http://purl.obolibrary.org/obo/UBERON_0001970"}],"attributes":[{"subj":"PD-UBERON-AE-B_T1","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T2","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T3","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T4","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T5","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T6","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T7","pred":"source","obj":"UBERON-AE"}]},{"project":"DisGeNet-2017-sample","denotations":[{"id":"T2142","span":{"begin":10,"end":15},"obj":"gene:2494"},{"id":"T2143","span":{"begin":19,"end":31},"obj":"disease:C0007102"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T2142","obj":"T2143"},{"id":"R2","pred":"associated_with","subj":"T2142","obj":"T2143"},{"id":"R3","pred":"associated_with","subj":"T2142","obj":"T2143"},{"id":"R4","pred":"associated_with","subj":"T2142","obj":"T2143"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T2142","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T2143","pred":"source","obj":"DisGeNet-2017-sample"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"25675535-0#10#15#gene2494","span":{"begin":10,"end":15},"obj":"gene2494"},{"id":"25675535-0#10#15#gene5026","span":{"begin":10,"end":15},"obj":"gene5026"},{"id":"25675535-0#19#31#diseaseC0007102","span":{"begin":19,"end":31},"obj":"diseaseC0007102"},{"id":"25675535-0#19#31#diseaseC0699790","span":{"begin":19,"end":31},"obj":"diseaseC0699790"},{"id":"25675535-0#19#31#diseaseC0007102","span":{"begin":19,"end":31},"obj":"diseaseC0007102"},{"id":"25675535-0#19#31#diseaseC0699790","span":{"begin":19,"end":31},"obj":"diseaseC0699790"},{"id":"25675535-4#101#106#gene2494","span":{"begin":611,"end":616},"obj":"gene2494"},{"id":"25675535-4#123#136#diseaseC0596263","span":{"begin":633,"end":646},"obj":"diseaseC0596263"},{"id":"25675535-5#75#80#gene2494","span":{"begin":755,"end":760},"obj":"gene2494"},{"id":"25675535-5#96#99#diseaseC1527249","span":{"begin":776,"end":779},"obj":"diseaseC1527249"}],"relations":[{"id":"10#15#gene249419#31#diseaseC0007102","pred":"associated_with","subj":"25675535-0#10#15#gene2494","obj":"25675535-0#19#31#diseaseC0007102"},{"id":"10#15#gene249419#31#diseaseC0699790","pred":"associated_with","subj":"25675535-0#10#15#gene2494","obj":"25675535-0#19#31#diseaseC0699790"},{"id":"10#15#gene249419#31#diseaseC0007102","pred":"associated_with","subj":"25675535-0#10#15#gene2494","obj":"25675535-0#19#31#diseaseC0007102"},{"id":"10#15#gene249419#31#diseaseC0699790","pred":"associated_with","subj":"25675535-0#10#15#gene2494","obj":"25675535-0#19#31#diseaseC0699790"},{"id":"10#15#gene502619#31#diseaseC0007102","pred":"associated_with","subj":"25675535-0#10#15#gene5026","obj":"25675535-0#19#31#diseaseC0007102"},{"id":"10#15#gene502619#31#diseaseC0699790","pred":"associated_with","subj":"25675535-0#10#15#gene5026","obj":"25675535-0#19#31#diseaseC0699790"},{"id":"10#15#gene502619#31#diseaseC0007102","pred":"associated_with","subj":"25675535-0#10#15#gene5026","obj":"25675535-0#19#31#diseaseC0007102"},{"id":"10#15#gene502619#31#diseaseC0699790","pred":"associated_with","subj":"25675535-0#10#15#gene5026","obj":"25675535-0#19#31#diseaseC0699790"},{"id":"101#106#gene2494123#136#diseaseC0596263","pred":"associated_with","subj":"25675535-4#101#106#gene2494","obj":"25675535-4#123#136#diseaseC0596263"},{"id":"75#80#gene249496#99#diseaseC1527249","pred":"associated_with","subj":"25675535-5#75#80#gene2494","obj":"25675535-5#96#99#diseaseC1527249"}],"attributes":[{"subj":"25675535-0#10#15#gene2494","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"25675535-0#10#15#gene5026","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"25675535-0#19#31#diseaseC0007102","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"25675535-0#19#31#diseaseC0699790","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"25675535-0#19#31#diseaseC0007102","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"25675535-0#19#31#diseaseC0699790","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"25675535-4#101#106#gene2494","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"25675535-4#123#136#diseaseC0596263","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"25675535-5#75#80#gene2494","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"25675535-5#96#99#diseaseC1527249","pred":"source","obj":"DisGeNET5_gene_disease"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"performance-test","color":"#93eccf","default":true},{"id":"PubmedHPO","color":"#ecb593"},{"id":"sentences","color":"#9b93ec"},{"id":"UBERON-AE","color":"#a5ec93"},{"id":"DisGeNet-2017-sample","color":"#ec93bf"},{"id":"DisGeNET5_gene_disease","color":"#93d9ec"}]}]}}