scholarly journals Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

2020 ◽  
Vol 21 (14) ◽  
pp. 5098 ◽  
Author(s):  
Jessica L. Bell ◽  
Sven Hagemann ◽  
Jessica K. Holien ◽  
Tao Liu ◽  
Zsuzsanna Nagy ◽  
...  

Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development and patient outcome, the role of RBPs in neuroblastoma is relatively unstudied. In order to elucidate novel RBPs involved in MYCN-amplified and other high-risk neuroblastoma subtypes, we performed differential mRNA expression analysis of RBPs in a large primary tumour cohort (n = 498). Additionally, we found via Kaplan–Meier scanning analysis that 685 of the 1483 tested RBPs have prognostic value in neuroblastoma. For the top putative oncogenic candidates, we analysed their expression in neuroblastoma cell lines, as well as summarised their characteristics and existence of chemical inhibitors. Moreover, to help explain their association with neuroblastoma subtypes, we reviewed candidate RBPs’ potential as biomarkers, and their mechanistic roles in neuronal and cancer contexts. We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma. Although not all RBPs appear suitable for drug design, or carry prognostic significance, we show that several RBPs have strong rationale for inhibition and mechanistic studies, representing an alternative, but nonetheless promising therapeutic strategy in neuroblastoma treatment.

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8252 ◽  
Author(s):  
Dingquan Yang ◽  
Yan Jiao ◽  
Yanqing Li ◽  
Xuedong Fang

Background MEX3A is an RNA-binding proteins (RBPs) that promotes the proliferation, invasion, migration and viability of cancer cells. The aim of this study was to explore the clinicopathological characteristics and prognostic significance of MEX3A mRNA expression in liver cancer. Methods RNA-Seq and clinical data were collected from The Cancer Genome Atlas (TCGA). Boxplots were used to represent discrete variables of MEX3A. Chi-square tests were used to analyze the correlation between clinical features and MEX3A expression. Receiver operating characteristic (ROC) curves were used to confirm diagnostic ability. Independent prognostic ability and values were assessed using Kaplan–Meier curves and Cox analysis. Results We acquired MEX3A RNA-Seq from 50 normal liver tissues and 373 liver cancer patients along with clinical data. We found that MEX3A was up-regulated in liver cancer which increased according to histological grade (p < 0.001). MEX3A showed moderate diagnostic ability for liver cancer (AUC = 0.837). Kaplan–Meier curves and Cox analysis revealed that the high expression of MEX3A was significantly associated with poor survival (OS and RFS) (p < 0.001). Moreover, MEX3A was identified as an independent prognostic factor of liver cancer (p < 0.001). Conclusions MEX3A expression shows promise as an independent predictor of liver cancer prognosis.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8509 ◽  
Author(s):  
Wei Li ◽  
Na Li ◽  
Lina Gao ◽  
Chongge You

Lung cancer is the top cause of carcinoma-associated deaths worldwide. RNA binding proteins (RBPs) dysregulation has been reported in various malignant tumors, and that dysregulation is closely associated with tumorigenesis and tumor progression. However, little is known about the roles of RBPs in lung adenocarcinoma (LUAD). In this study, we downloaded the RNA sequencing data of LUAD from The Cancer Genome Atlas (TCGA) database and determined the differently expressed RBPs between normal and cancer tissues. We then performed an integrative analysis to explore the expression and prognostic significance of these RBPs. A total of 164 differently expressed RBPs were identified, including 40 down-regulated and 124 up-regulated RBPs. Pathway and Gene ontology (GO) analysis indicated that the differently expressed RBPs were mainly related to RNA processing, RNA metabolic process, RNA degradation, RNA transport, splicing, localization, regulation of translation, RNA binding, TGF-beta signaling pathway, mRNA surveillance pathway, and aminoacyl-tRNA biosynthesis. Survival analysis revealed that the high expression of BOP1 or GNL3 or WDR12 or DCAF13 or IGF2BP3 or IGF2BP1 were associated with poor overall survival (OS). Conversely, overexpression of KHDRBS2/SMAD predicted high OS in these patients. ROC curve analysis showed that the eight hub genes with a better diagnostic accuracy to distinguish lung adenocarcinoma. The results provided novel insights into the pathogenesis of LUAD and the development of treatment targets and prognostic molecular markers.


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