The impact of microRNA expression on cellular proliferation

Abstract

A s an important class of non-coding regulatory RNA s, microRNA s (miRNAs) play a key role in a range of biological processes. These molecules serve as post-transcriptional regulators of gene expression and their regulatory activity has been implicated in disease pathophysiology and pharmacological traits. We sought to investigate the impact of miRNAs on cellular proliferation to gain insight into the molecular basis of complex traits that depend on cellular growth, including, most prominently, cancer. We examined the relationship between miRNA expression and intrinsic cellular growth (iGrowth) in the HapMap lymphoblastoid cell lines derived from individuals of different ethnic backgrounds. We found a substantial enrichment for miRNAs (53 miRNAs, FDR < 0.05) correlated with cellular proliferation in pooled CEU (Caucasian of northern and western European descent) and YRI (individuals from Ibadan, Nigeria) samples. Specifically, 119 miRNAs (59 %) were significantly correlated with iGrowth in YRI; of these miRNAs, 18 were correlated with iGrowth in CEU. To gain further insight into the effect of miRNAs on cellular proliferation in cancer, we showed that over-expression of miR-22, one of the top iGrowth-associated miRNAs, leads to growth inhibition in an ovarian cancer cell line (SKOV3). Furthermore, over-expression of miR-22 down-regulates the expression of its target genes (MXI1 and SLC25A37) in this ovarian cancer cell line, highlighting an miRNA-mediated regulatory network potentially important for cellular proliferation. Importantly, our study identified miRNAs that can be used as molecular targets in cancer therapy.

Circulating non-coding RNAs in recurrent and metastatic ovarian cancer

“…The outcome is a variety of degrees of protein synthesis control as opposed to the simpler idea of a miRNA just blocking a mRNA activity. As well as being important components of the control of protein synthesis in healthy cells [85] , ceRNAs appear to play an important role in tumor cells and tissues [86][87][88] with modification of miRNA concentrations possibly resulting in dysregulation of either oncogenes and/or of tumor suppressors [89] . ceRNA involvement in cancer has been well-reviewed by a number of scientists, e.g., Karreth & Pandolfi [90] , Tay et al [91] , Qi et al [87] , Chan and Tay [6] .…”

mir-23b: A New Molecular Marker For Neonatal Sepsis In Haemoculture

“…MicroRNAs (miRNAs), a class of small single-stranded non-coding regulatory RNAs of about 19 to 22 nucleotides, are involved in a wide range of biological processes and have opened a new window of hope to diagnose, and even treat, various diseases. miRNA binds to specific mRNA molecules to inhibit the expression of target genes or to degrade mRNA, which then contributes to cell proliferation, differentiation, development, metabolism, apoptosis and other physiological activities [11,12]. Given their role in various cellular processes, recent studies have shown how miRNAs may have the potential to be an early biomarker in a number of diseases, including sepsis [13].…”

miR-182 controls cell growth in gastrointestinal stromal tumors by negatively regulating CYLD expression

“…More than 60% of protein-coding genes have been computationally predicted as miRNA targets, based on evolutionarily conserved base-pairing between mRNAs and the seed sequences of miRNAs (7). It is evident that miRNAs play essential roles in the regulation of multiple cellular processes, including proliferation (8), apoptosis (9), differentiation (10) and the cell cycle (11). The abnormal expression of miRNAs contributes to the pathogenesis of multiple human diseases (12), including cancer (13,14).…”