Chapter 17 - Modulation of Expression of miRNAs for Therapeutic Effects in Human Malignant Neuroblastoma

Abstract

The small non-coding RNAs are called microRNAs or miRNAs that play key roles in mRNA silencing as well as in post-transcriptional regulation of gene expression in eukaryotic cells. The finding of miRNAs as negative regulators of gene expression at post-transcriptional level have added a new layer to the fine regulation of cell signaling mechanisms in human health and disease. Many miRNAs are known to play key roles in tumor biology. The actions of miRNAs may produce oncogenic or tumor suppressive effects. A specific miRNA may act as an oncogenic miRNA or a tumor suppressor miRNA depending on the tumor. The pathogenesis of human malignant neuroblastoma, which is a deadly childhood tumor, is now known to be associated with upregulation of oncogenic miRNAs and down regulation of tumor suppressor miRNAs. Upregulation of oncogenic miRNAs drives the growth of human malignant neuroblastoma by avoiding cell cycle arrest, differentiation, and apoptotic death. On the other hand, the down regulation of tumor suppressor miRNAs promotes cell proliferation, hypoxia, autophagy, multidrug resistance, migration, invasion, angiogenesis, and metastasis in human malignant neuroblastoma. So, inhibition of expression of specific oncogenic miRNAs and promotion of expression of tumor suppressor miRNAs may provide novel therapeutic opportunities to induce cell cycle arrest, differentiation, and apoptosis in human malignant neuroblastoma cells in vitro as well as in vivo. The success of modulation of expression of miRNAs in preclinical models of human malignant neuroblastoma may eventually be translated to the clinics for successful treatment of neuroblastoma patients in the future.