Silencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells

Abstract

Signal transduction through the IGF axis is implicated in proliferation, differentiation and survival during development and adult life. The IGF axis includes the IGF binding proteins (IGFBPs) that bind IGFs with high affinity and modulate their activity. In neuroblastoma (NB), a malignant childhood tumor, we found that IGFBP-5 is frequently expressed. Since NB is an IGF2-sensitive tumor, we investigated the relevance and the function of endogenous IGFBP-5 in LAN-5 and in SY5Y(N) cell lines transfected with micro and small interfering RNAs directed to IGFBP-5 mRNA. Cells in which IGFBP-5 expression was suppressed were growth-inhibited and more prone to apoptosis than the parental cell line and controls. Apoptosis was further enhanced by X-ray irradiation. The ability of these cells to undergo neuronal differentiation was impaired after IGFBP-5 inhibition but the effect was reversed by exposure to recombinant IGFBP-5. Together, these data demonstrate the importance of IGFBP-5 for NB cell functions and suggest that IGFBP-5 might serve as a novel therapeutic target in NB.

Concise Review: MicroRNA Expression in Multipotent Mesenchymal Stromal Cells

“…Few target genes that are regulated by microRNAs are currently documented, but the ones identified have important roles in apoptosis, homeobox regulation, development [30,[97][98][99][100][101], cell growth and apoptosis [13,14], viral infection [15,19], and human cancer [81,[102][103][104]. This type of gene control represents a new regulatory mechanism and is predicted to affect many crucial cellular processes, including developmental programs.…”

Tumor-Associated Retinal Astrocytes Promote Retinoblastoma Cell Proliferation Through Production of IGFBP-5

“…In support of this possibility, IGFBP5 RNA is expressed in the normal retina and is up-regulated in angiomatous tufts during retinal neovascularization. 52 Moreover, an oncogenic role of IGFBP-5 is not without precedent, as IGFBP-5 is overexpressed in diverse cancers, 53,54 is required for neuroblastoma anchorage-independent growth, 51 and enhances the in vivo tumorigenic potential of androgen-dependent prostate cancer cells. 49,50 If retinal astrocytes were indeed to contribute to retinoblastoma tumorigenesis, then this could have several important ramifications.…”

MicroRNAs: recently discovered key regulators of proliferation and apoptosis in animal cells

“…Transfection of specifically designed miRNAs against the 3¢ UTR of IGFBP-5 were able to both decrease proliferation and induce apoptosis in neuroblastoma cells (Tanno et al 2005).…”