MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

Abstract

Neuroblastoma (NB) is one of the most common forms of cancer in children, accounting for 15% of pediatric cancer deaths. The clinical course of these tumors is highly variable and is dependent on such factors as age at presentation, stage, ploidy and genomic abnormalities. Hemizygous deletion of chromosome 1p occurs in approximately 30% of advanced stage tumors, is associated with a poor prognosis, and likely leads to the loss of one or more tumor suppressor genes. We show here that microRNA (miRNA)-34a (1p36.23) is generally expressed at lower levels in unfavorable primary NB tumors and cell lines relative to normal adrenal tissue and that reintroduction of this miRNA into three different NB cell lines causes a dramatic reduction in cell proliferation through the induction of a caspase-dependent apoptotic pathway. As a potential mechanistic explanation for this observation, we demonstrate that miR-34a directly targets the messenger ribonucleic acid (mRNA) encoding E2F3 and significantly reduces the levels of E2F3 protein, a potent transcriptional inducer of cell-cycle progression. Furthermore, miR-34a expression increases during retinoic acidinduced differentiation of the SK-N-BE cell line, whereas E2F3 protein levels decrease. Thus, adding to the increasing role of miRNAs in cancer, miR-34a may act as a suppressor of NB tumorgenesis.

Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer

“…Axl-mRNA and Axl protein expression significantly inversely correlated with the miR-34a expression, and cell invading capacity positively correlated with Axl protein amounts and inversely with miR-34a expression. In general, our findings strongly support the existing literature that Axl is an oncogene and miR-34a is a tumor suppressor (Hafizi and Dahlback, 2006;Vajkoczy et al, 2006;Bommer et al, 2007;Welch et al, 2007;Mudduluru et al, 2010). Previous studies reported that miR-34a can inhibit cell cycle (CCNE2, CDK4, CDK6, Cyclin E2 and E2F5), anti-apoptotic protein (BCL2) and invasion (MET) inducing genes (Bommer et al, 2007;Chang et al, 2007;He et al, 2007;Raver-Shapira et al, 2007).…”

Role of miR-143 targeting KRAS in colorectal tumorigenesis

“…Next, the cell viability of each treatment was determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay as described previously (Welch et al, 2007). As shown in Figure 3g, Lovo cells treated with anti-miR-143 oligonucleotides had a significant increase in cell viability compared with the scrambled antisense oligonucleotides transfected cells.…”

TBHP-induced oxidative stress alters microRNAs expression in mouse testis

“…[ 49,10,39,54,55,8] miR-181b Function as tumor suppressors; triggering growth inhibition; inducing apoptosis in glioma cells (target genes: PTEN and Rsbn1).…”