Genomic analyses reveal broad impact of miR-137 on genes associated with malignant transformation and neuronal differentiation in glioblastoma cells.
miR-137 plays critical roles in the nervous system and tumor development; an increase in its expression is required for neuronal differentiation while its reduction is implicated in gliomagenesis. To evaluate the potential of miR-137 in glioblastoma therapy, we conducted genome-wide target mapping in glioblastoma cells by measuring the level of association between PABP and mRNAs in cells transfected with miR-137 mimics vs. controls via RIPSeq. Impact on mRNA levels was also measured by RNASeq. By combining the results of both experimental approaches, 1468 genes were found to be negatively impacted by miR-137--among them, 595 (40%) contain miR-137 predicted sites. The most relevant targets include oncogenic proteins and key players in neurogenesis like c-KIT, YBX1, AKT2, CDC42, CDK6 and TGFβ2. Interestingly, we observed that several identified miR-137 targets are also predicted to be regulated by miR-124, miR-128 and miR-7, which are equally implicated in neuronal differentiation and gliomagenesis. We suggest that the concomitant increase of these four miRNAs in neuronal stem cells or their repression in tumor cells could produce a robust regulatory effect with major consequences to neuronal differentiation and tumorigenesis.
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Saleh
S
Tamim
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Dat T
DT
Vo
Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.
Philip J
PJ
Uren
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Mei
M
Qiao
Basic Science Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
Eckart
E
Bindewald
Basic Science Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
Wojciech K
WK
Kasprzak
Center for Cancer Research Nanobiology Program, National Cancer Institute, Frederick, Maryland, California.
Bruce A
BA
Shapiro
Department of Clinical Analyses and Toxicology, Institute of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Helder I
HI
Nakaya
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Suzanne C
SC
Burns
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Patricia R
PR
Araujo
Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
Ichiro
I
Nakano
Epicentre (An Illumina Company), Madison, Wisconsin, United States of America.
Agnes J
AJ
Radek
Epicentre (An Illumina Company), Madison, Wisconsin, United States of America.
Scott
S
Kuersten
Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.
Andrew D
AD
Smith
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Luiz O F
LO
Penalva
D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins