MicroRNA biogenesis and cellular proliferation.
MicroRNA biogenesis and cellular proliferation.
复制标题
DOI：
10.1016/j.trsl.2015.01.012
复制
发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Huang RS
中科院分区：
文献类型：
--
作者：
Lenkala D;Gamazon ER;LaCroix B;Im HK;Huang RS
鉴于 microRNA (miRNA) 在生理、发育和病理过程中的基本作用，我们假设参与 miRNA 生物发生的基因有助于人类复杂的性状。对于十三个这样的基因，我们评估了转录与两类复杂性状之间的关系，即一组淋巴母细胞系中的细胞生长和对各种化疗药物的敏感性。我们发现蛋白质 argonaute-2 (AGO2) 表达与细胞生长速率之间存在高度显着的相关性（Bonferroni 调整后的 p < 0.05），并报告了其他 miRNA 生物发生基因，这些基因与细胞生长速率或化疗敏感性存在暗示关联。发现 AGO2 表达与多种药物敏感性表型相关。此外，AGO2 的小干扰 RNA (siRNA) 敲低导致卵巢癌细胞系 (OVCAR3) 的细胞生长受到抑制，支持了该 miRNA 生物合成基因在癌细胞增殖中的作用。表达数量性状基因座作图表明，可能调节 AGO2 表达的遗传变异（以单核苷酸多态性 (SNP) 和拷贝数变异 (CNV) 的形式）可能对细胞生长依赖性复杂表型产生下游影响。
Given the fundamental roles of microRNAs (miRNAs) in physiological, developmental and pathological processes, we hypothesized that genes involved in miRNA biogenesis contribute to human complex traits. For thirteen such genes, we evaluated the relationship between transcription and two classes of complex traits, namely cellular growth and sensitivity to various chemotherapeutic agents in a set of lymphoblastoid cell lines. We found a highly significant correlation between protein argonaute-2 (AGO2) expression and cellular growth rate (Bonferroni-adjusted p < 0.05), and report additional miRNA biogenesis genes with suggestive associations with either cellular growth rate or chemotherapeutic sensitivity. AGO2 expression was found to be correlated with multiple drug sensitivity phenotypes. Furthermore, small interfering RNA (siRNA) knockdown of AGO2 resulted in cellular growth inhibition in an ovarian cancer cell line (OVCAR3), supporting the role of this miRNA biogenesis gene in cell proliferation in cancer cells. Expression quantitative trait loci mapping indicated that genetic variation (in the form of both single nucleotide polymorphisms (SNPs) and copy number variations (CNVs)) that may regulate the expression of AGO2 can have downstream effects on cellular-growth-dependent complex phenotypes.