In silico analyses reveal new putative Breast Cancer RNA-binding proteins

Abstract

Breast cancer (BC) is the leading cause of cancer-associated death among women worldwide. Despite treatment efforts, advanced BC with distant organ metastases is considered incurable. A better understanding of BC molecular processes is therefore of great interest to identify new therapeutic targets. Although large-scale efforts, such as The Cancer Genome Atlas (TCGA), have completely redefined cancer drug development, diagnosis, and treatment, additional key aspects of tumor biology remain to be discovered. In that respect, post-transcriptional regulation of tumorigenesis represents an understudied aspect of cancer research. As key regulators of this process, RNA-binding proteins (RBPs) are emerging as critical modulators of tumorigenesis but only few have defined roles in BC. To unravel new putative BC RBPs, we have performed in silico analyses of all human RBPs in three major cancer databases (TCGA-Breast Invasive Carcinoma, the Human Protein Atlas, and the Cancer Dependency Map project) along with complementary bioinformatics resources (STRING protein-protein interactions and the Network of Cancer Genes 6.0). Thus, we have identified six putative BC progressors (MRPL13, SCAMP3, CDC5L, DARS2, PUF60, and PLEC), and five BC suppressors RBPs (SUPT6H, MEX3C, UPF1, CNOT1, and TNKS1BP1). These proteins have never been studied in BC but show similar cancer-associated features than well-known BC proteins. Further research should focus on the mechanisms by which these proteins promote or suppress breast tumorigenesis, holding the promise of new therapeutic pathways along with novel drug development strategies.

TCGA Pan-Cancer Genomic Analysis of Alternative Lengthening of Telomeres (ALT) Related Genes

“…PPi networks are useful resources to understand how proteins interact between them in the cell [ 38 ], hence, the STRING database [ 32 ] was used to observe the interactions of 103 proteins. By using an interaction score of highest confidence (0.9) [ 33 ], a network was constructed; additionally, the most significant pathways ( p < 0.001) were selected and marked with different colors in the nodes ( Figure 5 a). As a result, 68% of the proteins in the network are essential for DNA binding; 59% for DNA metabolic process; 47% for DNA repair; 23% for telomere organization and maintenance; 12% for telomeric DNA binding; and 22% are involved in DNA Double-Strand Break Repair, HDR and HDR through Homologous Recombination (HRR).…”

“…In order to predict the interactions among the ALT-related proteins, the STRING database ( ) was used. An interaction score of 0.9 (highest confidence) was set in the system configuration [ 32 , 33 ] and the most significant signaling pathways ( p < 0.001) related to ALT were selected and differentiated by colors in the network.…”

OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine

“…17 OncoOmics BC essential genes were involved in DNA repair 64 . RBPs are key players in post-transcriptional events and are emerging as critical modulators in BC [100][101][102] . Bioinformatics profiling of tumors have revealed the landscape of alterations in RBPs across cancer types [103][104][105][106] .…”

Oncology and Pharmacogenomics Insights in Polycystic Ovary Syndrome: An Integrative Analysis

“…The knowledge of protein alteration in malignant transformation is currently growing for the discovery of biomarkers ( 66 ). Hereafter, we analyze the genomic alterations, transcriptional profiles, and protein expression changes of PRG in EC, OC, and BC as similarly performed in other studies ( 67 , 68 ).…”