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Non-coding RNAs as modulators of radioresponse in triple-negative breast cancer: a systematic review
Maria Vitoria Tofolo1, Fernanda Costa Brandão Berti1, Emanuelle Nunes-Souza1
1Research Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Av. Silva Jardim, 1632, Curitiba, 80250-060, Brazil.
Abstract:
Triple-negative breast cancer (TNBC), characterized by high invasiveness, is associated with poor prognosis and elevated mortality rates. Despite the development of effective therapeutic targets for TNBC, systemic chemotherapy and radiotherapy (RdT) remain prevalent treatment modalities. One notable challenge of RdT is the acquisition of radioresistance, which poses a significant obstacle in achieving optimal treatment response. Compelling evidence implicates non-coding RNAs (ncRNAs), gene expression regulators, in the development of radioresistance. This systematic review focuses on describing the role, association, and/or involvement of ncRNAs in modulating radioresponse in TNBC. In adhrence to the PRISMA guidelines, an extensive and comprehensive search was conducted across four databases using carefully selected entry terms. Following the evaluation of the studies based on predefined inclusion and exclusion criteria, a refined selection of 37 original research articles published up to October 2023 was obtained. In total, 33 different ncRNAs, including lncRNAs, miRNAs, and circRNAs, were identified to be associated with radiation response impacting diverse molecular mechanisms, primarily the regulation of cell death and DNA damage repair. The findings highlighted in this review demonstrate the critical roles and the intricate network of ncRNAs that significantly modulates TNBC's responsiveness to radiation. The understanding of these underlying mechanisms offers potential for the early identification of non-responders and patients prone to radioresistance during RdT, ultimately improving TNBC survival outcomes.
Insights
Non-coding RNAs (ncRNAs) play a critical role in triple-negative breast cancer (TNBC) radioresistance. Understanding these ncRNAs can help predict treatment response and improve outcomes for TNBC patients undergoing radiotherapy (RdT).
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) is highly invasive with poor prognosis.
- Radiotherapy (RdT) is a common treatment, but radioresistance is a major challenge.
- Non-coding RNAs (ncRNAs) are implicated in regulating gene expression and treatment resistance.
Purpose of the Study:
- To systematically review the role of ncRNAs in modulating radioresponse in TNBC.
- To identify specific ncRNAs associated with radiation sensitivity or resistance in TNBC.
- To explore the molecular mechanisms by which ncRNAs affect TNBC response to RdT.
Main Methods:
- Systematic literature review adhering to PRISMA guidelines.
- Comprehensive search across four databases using selected keywords.
- Inclusion/exclusion criteria applied to 37 original research articles (up to October 2023).
Main Results:
- 33 distinct ncRNAs (lncRNAs, miRNAs, circRNAs) were identified as associated with radiation response in TNBC.
- These ncRNAs impact key molecular mechanisms, including cell death regulation and DNA damage repair.
- An intricate network of ncRNAs significantly modulates TNBC responsiveness to RdT.
Conclusions:
- ncRNAs are critical regulators of radioresistance in triple-negative breast cancer.
- Understanding ncRNA networks offers potential for identifying non-responders to RdT.
- Targeting ncRNAs may improve treatment strategies and survival outcomes for TNBC patients.
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Types of RNA
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
lncRNA - Long Non-coding RNAs
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
MicroRNAs
Experimental RNAi
Regulation of Expression at Multiple Steps

