Abstract
Given the fundamental roles of microRNAs (miRNAs) in physiological, developmental, and pathologic processes, we hypothesized that genes involved in miRNA biogenesis contribute to human complex traits. For 13 such genes, we evaluated the relationship between transcription and 2 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 argonaute RNA-induced silencing complex catalytic component 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 knockdown of AGO2 resulted in cellular growth inhibition in an ovarian cancer cell line (OVCAR-3), 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 and copy number variations) that may regulate the expression of AGO2 can have downstream effects on cellular growth-dependent complex phenotypes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 145-151 |
| Number of pages | 7 |
| Journal | Translational Research |
| Volume | 166 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1 2015 |
| Externally published | Yes |
Bibliographical note
Funding Information:This study was supported by the National Institute of Health/National Cancer Institute ( NIH / NCI) grant R21 CA139278 and NIH / NIGMS (National Institute of General Medical Sciences) grant UO1GM61393 . R.S.H. also received support from the NIH / NIGMS grant K08GM089941 , Circle of Service Foundation Early Career Investigator award , University of Chicago Cancer Center support grant (# P30 CA14599 ), Breast Cancer Specialized Programs of Research Excellence Career Development Award ( CA125183 ) a Conquer Cancer Foundation of American Society of Clinical Oncology Translational Research Professorship award in the memory of Merrill J. Egorin, MD, and pilot grant from NIH / NCATS (National Center for Advancing Translational Sciences) grant UL1RR024999 . H.K.I. received support from the NIH / NCI K12CA139160 and NIH / NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) P30 DK020595 .
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© 2015 Elsevier Inc. All rights reserved.
