Linked Life Data

20647762

Source:http://linkedlifedata.com/resource/pubmed/id/20647762

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2010-8-16
pubmed:abstractText
Glioblastoma, the most common and aggressive primary brain tumor, is rapidly growing and highly infiltrative. Incomplete knowledge of the molecular biology, genetics, causes and cellular origin of these tumors may limit the development of improved therapeutics. A major and fundamental advance in recent years has been the identification of microRNAs as highly conserved regulators of gene expression. Here we will discuss further our recently published data on the role of miR-451 in the biology of glioblastoma. We initially identified miR-451 due to its downregulation in a glioma cell migration assay. We then found that by targeting the LKB1 kinase complex miR-451 suppresses the activity of downstream protein kinases including the major energy biosensor AMPK. MiR-451 levels are regulated by glucose; under conditions of abundant energy miR-451 expression is high, and the suppression of AMPK signaling allows cells to maintain elevated proliferation rates via unrestrained mTOR activation. Under conditions of glucose withdrawal, miR-451 downregulation is necessary for AMPK pathway activation, leading to suppressed proliferation rates, increased cell survival and migration. We also identified a potential feedback loop between LKB1 and miR-451, which allows a sustained and robust response to glucose deprivation. This data will be discussed in the context of potential biological significance and therapeutic implications.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AMP-activated protein kinase kinase, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm, http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins, http://linkedlifedata.com/resource/pubmed/chemical/CAB39L protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Glucose, http://linkedlifedata.com/resource/pubmed/chemical/MIRN451 microRNA, human, http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/STK11 protein, human
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2742-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
microRNA-451: A conditional switch controlling glioma cell proliferation and migration.
pubmed:affiliation
Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't