RNA Binding Protein-Mediated Post-Transcriptional Gene Regulation in Medulloblastoma

Abstract

Medulloblastoma, the most common malignant brain tumor in children, is a disease whose mechanisms are now beginning to be uncovered by high-throughput studies of somatic mutations, mRNA expression patterns, and epigenetic profiles of patient tumors. One emerging theme from studies that sequenced the tumor genomes of large cohorts of medulloblastoma patients is frequent mutation of RNA binding proteins. Proteins which bind multiple RNA targets can act as master regulators of gene expression at the post-transcriptional level to co-ordinate cellular processes and alter the phenotype of the cell. Identification of the target genes of RNA binding proteins may highlight essential pathways of medulloblastomagenesis that cannot be detected by study of transcriptomics alone. Furthermore, a subset of RNA binding proteins are attractive drug targets. For example, compounds that are under development as anti-viral targets due to their ability to inhibit RNA helicases could also be tested in novel approaches to medulloblastoma therapy by targeting key RNA binding proteins. In this review, we discuss a number of RNA binding proteins, including Musashi1 (MSI1), DEAD (Asp-Glu-Ala-Asp) box helicase 3 X-linked (DDX3X), DDX31, and cell division cycle and apoptosis regulator 1 (CCAR1), which play potentially critical roles in the growth and/or maintenance of medulloblastoma.

LncRNA FENDRR attenuates adriamycin resistance via suppressing MDR1 expression through sponging HuR and miR‐184 in chronic myelogenous leukaemia cells

“…In our study, we found that FENDRR and MDR1 3 0 UTR contain several AU-rich elements (AREs) sequences, which interact with RNA-binding protein (RBP), suggesting that FENDRR and MDR1 may be subjected to post-transcriptional regulation. Previous studies have indicated that RBP can bind to ARE sequences of mRNA for stabilizing and/or regulating their translation [44]. On the basis of our findings, we confirmed that HuR can stabilize the mRNA of FENDRR and MDR1.…”

RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation

“…For example, ENDOG, mutated in family B (p.R111fs), is a DNase involved in mediating caspase-independent apoptosis 21. DDX31, a RNA-binding protein mutated in family C (p.L367fs), is frequently mutated in medulloblastoma,22 and a germline truncating mutation was observed in a patient with sporadic CRC 23. Family D carries a RGS19 nonsense mutation (p.Q89X), a gene involved in regulating G-protein signalling and autophagy in intestinal cells 24.…”

ceRNA in cancer: possible functions and clinical implications

“…RBPs participate in multiple post-transcriptional regulations, such as RNA splicing, stability and degradation 42 43. Accordingly, they might serve as potential mediators of ceRNA activity in several ways.…”