Genome-wide miRNA expression profiling of human lymphoblastoid cell lines identifies tentative SSRI antidepressant response biomarkers.
OBJECTIVE
Over 30% of patients with major depression do not respond well to first-line treatment with selective serotonin reuptake inhibitors (SSRIs). Using genome-wide expression profiling of human lymphoblastoid cell lines (LCLs) CHL1 was identified as a tentative SSRI sensitivity biomarker. This study reports on miRNAs implicated in SSRI sensitivity of LCLs.


METHODS
Eighty LCLs were screened from healthy adult female individuals for growth inhibition by paroxetine. Eight LCLs exhibiting high or low sensitivities to paroxetine were chosen for genome-wide expression profiling with miRNA microarrays.


RESULTS
The miRNA miR-151-3p had 6.7-fold higher basal expression in paroxetine-sensitive LCLs. This corresponds with lower expression of CHL1, a target of miR-151-3p. The additional miRNAs miR-212, miR-132, miR-30b*, let-7b and let-7c also differed by >1.5-fold (p < 0.05) between the two LCL groups.


CONCLUSIONS
The potential value of these miRNAs as tentative SSRI response biomarkers awaits validation with lymphocyte samples of major depression patients.
Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Keren
K
Oved
Ayelet
A
Morag
Metsada
M
Pasmanik-Chor
Varda
V
Oron-Karni
Noam
N
Shomron
Moshe
M
Rehavi
Julia C
JC
Stingl
David
D
Gurwitz
D054316:Biomarkers, Pharmacological; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D017374:Paroxetine / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D054316:Biomarkers, Pharmacological; D015815:Cell Adhesion Molecules; D035683:MicroRNAs; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; C490650:CHL1 protein, human; C548886:MIRN151a microRNA, human