Comprehensive Analysis of RNA-Binding Protein-Related lncRNA in Breast Invasive Carcinoma

RNA-binding proteins (RBPs), which form complexes or single/multiple RNA-binding domains, have a functional role in regulating and determining the function or stability of the bound RNAs in various cancers, including breast invasive carcinoma (BRCA). However, the biological functions and clinical implications of RBP-related long noncoding RNAs (lncRNAs) in BRCA remain largely unknown.

Herein, we first identified and characterized RBP-related lncRNAs in BRCA. Then we built an RBP-related lncRNA signature (RBPLSig) and explored the clinical evaluation and prediction performance of the RBPLSig by bioinformatic analysis. In addition, to optimize treatment plans, prediction online tools was developed to predict the patient survival rate. Lastly, to verify the function of lncRNA WAC antisense RNA 1 (WAC-AS1), the experiments such as Quantitative real-time PCR (qRT-PCR), lncRNA knockdown, CCK-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining were performed. We also gained the potential mechanisms of the druggable compounds of the WAC-AS1 related RBP gene, putative NSUN6, using molecular docking.

The results showed that RBPLSig, as an independent prognostic factor for BRCA patients, was involved in numerous malignancy-associated immunoregulatory pathways. We found different immune statuses and responses to immunotherapy, chemotherapy, and targeted therapy between the high- and low-risk groups stratified by RBPLSig.

Our data broaden the comprehensive understanding of the biological functions of RBP-related lncRNAs, and demonstrate a novel and independent RBPLSig to assess prognosis and the immune microenvironment, thus helping to guide treatment decisions for BRCA.