人类淋巴母细胞系全基因组 miRNA 表达谱分析确定了暂定的 SSRI 抗抑郁药反应生物标志物。

Genome-wide miRNA expression profiling of human lymphoblastoid cell lines identifies tentative SSRI antidepressant response biomarkers.

机构信息

Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

出版信息

Pharmacogenomics. 2012 Jul;13(10):1129-39. doi: 10.2217/pgs.12.93.

DOI:10.2217/pgs.12.93

PMID:22909203

Abstract

AIM

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.

CONCLUSION

The potential value of these miRNAs as tentative SSRI response biomarkers awaits validation with lymphocyte samples of major depression patients.

摘要

目的

超过 30%的重度抑郁症患者对一线治疗药物选择性 5-羟色胺再摄取抑制剂（SSRIs）的反应不佳。利用人类淋巴母细胞系（LCL）CHL1 的全基因组表达谱分析，发现其可作为 SSRI 敏感性的候选生物标志物。本研究报告了与 LCL 的 SSRI 敏感性相关的 miRNAs。

方法

从健康成年女性个体的 80 个 LCL 中筛选出对帕罗西汀的生长抑制作用。选择对帕罗西汀敏感或不敏感的 8 个 LCL 进行 miRNA 微阵列的全基因组表达谱分析。

结果

miR-151-3p 在帕罗西汀敏感的 LCL 中基础表达高出 6.7 倍。这与 miR-151-3p 的靶标 CHL1 的表达降低相对应。另外两个 miRNA（miR-212、miR-132、miR-30b*、let-7b 和 let-7c）在两组 LCL 之间也存在 >1.5 倍的差异（p<0.05）。