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RNA-binding protein NONO contributes to cancer cell growth and confers drug resistance as a theranostic target in TNBC
- Source :
- Theranostics
- Publication Year :
- 2020
- Publisher :
- Ivyspring International Publisher, 2020.
-
Abstract
- Breast cancer (BC) is one of the most common cancers in women. TNBC (Triple-negative breast cancer) has limited treatment options and still lacks viable molecular targets, leading to poor outcomes. Recently, RNA-binding proteins (RBPs) have been shown to play crucial roles in human cancers, including BC, by modulating a number of oncogenic phenotypes. This suggests that RBPs represent potential molecular targets for BC therapy. Methods: We employed genomic data to identify RBPs specifically expressed in TNBC. NONO was silenced in TNBC cell lines to examine cell growth, colony formation, invasion, and migration. Gene expression profiles in NONO-silenced cells were generated and analyzed. A high-throughput screening for NONO-targeted drugs was performed using an FDA-approved library. Results: We found that the NONO RBP is highly expressed in TNBC and is associated with poor patient outcomes. NONO binds to STAT3 mRNA, increasing STAT3 mRNA levels in TNBC. Surprisingly, NONO directly interacts with STAT3 protein increasing its stability and transcriptional activity, thus contributing to its oncogenic function. Importantly, high-throughput drug screening revealed that auranofin is a potential NONO inhibitor and inhibits cell growth in TNBC. Conclusions: NONO is an RBP upstream regulator of both STAT3 RNA and protein levels and function. It represents an important and clinically relevant promoter of growth and resistance of TNBCs. NONO is also therefore a potential therapeutic target in TNBC.
- Subjects :
- STAT3 Transcription Factor
0301 basic medicine
Medicine (miscellaneous)
Apoptosis
Triple Negative Breast Neoplasms
RNA-binding protein
Biology
Theranostic Nanomedicine
STAT3
03 medical and health sciences
0302 clinical medicine
RBP
Cell Movement
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
Gene expression
Humans
Precision Medicine
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Cell Proliferation
Drug Carriers
Messenger RNA
Cell growth
RNA-Binding Proteins
RNA
Genomics
Phenotype
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
030104 developmental biology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer cell
Cancer research
biology.protein
Nanoparticles
Female
Drug Screening Assays, Antitumor
Auranofin
NONO
TNBC
Signal Transduction
Research Paper
Subjects
Details
- ISSN :
- 18387640
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....119fc75a722b120cef5a751bba0a956b