TY - JOUR
T1 - MicroRNA biogenesis and cellular proliferation
AU - Lenkala, Divya
AU - Gamazon, Eric R.
AU - Lacroix, Bonnie
AU - Im, Hae Kyung
AU - Huang, R. Stephanie
N1 - Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.trsl.2015.01.012
DO - 10.1016/j.trsl.2015.01.012
M3 - Article
C2 - 25724890
AN - SCOPUS:84937639994
SN - 1931-5244
VL - 166
SP - 145
EP - 151
JO - Translational Research
JF - Translational Research
IS - 2
ER -
