MicroRNA biogenesis and cellular proliferation

Divya Lenkala, Eric R. Gamazon, Bonnie Lacroix, Hae Kyung Im, R. Stephanie Huang

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 languageEnglish (US)
Pages (from-to)145-151
Number of pages7
JournalTranslational Research
Volume166
Issue number2
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

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