Breast Cancer: Current Research
Open Access

Non-coding RNAs (ncRNAs); Circular RNAs (circRNAs); Long non-coding RNAs (lncRNAs); Messenger RNAs (mRNAs); Breast cancer management; MicroRNAs (miRNAs); Epithelial-to-mesenchymal transition (EMT); Metastasis

Introduction

Breast cancer remains a significant health burden worldwide, driving ongoing research efforts to unravel its molecular underpinnings and identify novel therapeutic targets. While protein-coding genes have traditionally received the spotlight in cancer research, non-coding RNAs (ncRNAs) have emerged as key players in breast cancer pathogenesis. This article delves into the impact of ncRNAs on breast cancer, shedding light on their diverse roles and therapeutic implications [1].

Methodology

The Diversity of Non-Coding RNAs: ncRNAs encompass a diverse array of RNA molecules that do not encode proteins but instead regulate gene expression and cellular processes at multiple levels. Among the major classes of ncRNAs are microRNAs (miRNAs), which post-transcriptionally regulate gene expression by targeting messenger RNAs (mRNAs) for degradation or translational repression. Long non-coding RNAs (lncRNAs) are longer than 200 nucleotides and participate in various biological processes, including chromatin remodeling, transcriptional regulation and RNA splicing. Circular RNAs (circRNAs) are covalently closed RNA molecules formed by back-splicing events and have been implicated in modulating gene expression by acting as miRNA sponges or interacting with RNA-binding proteins [2].

Dysregulation of Non-Coding RNAs in Breast Cancer: The dysregulated expression of ncRNAs is a hallmark of breast cancer, contributing to tumor initiation, progression, and metastasis. Numerous studies have identified aberrantly expressed miRNAs, lncRNAs, and circRNAs associated with breast cancer subtypes, disease stage, and clinical outcomes [3]. Dysregulated ncRNAs can function as oncogenes or tumor suppressors by modulating key signaling pathways involved in cell proliferation, apoptosis, migration, and invasion. For example miR-21, an oncogenic miRNA, promotes breast cancer progression by targeting tumor suppressor genes such as PTEN and PDCD4. Conversely, tumor-suppressive miRNAs such as members of the miR-200 family inhibit epithelial-to-mesenchymal transition (EMT) and metastasis by targeting ZEB1 and ZEB2 transcription factors [4]. Similarly, dysregulated lncRNAs, such as HOTAIR and MALAT1, have been implicated in breast cancer metastasis and poor prognosis.

Diagnostic and Prognostic Implications: The dysregulated expression of ncRNAs in breast cancer holds promise as diagnostic and prognostic biomarkers. The unique expression patterns of specific miRNAs, lncRNAs and circRNAs in breast cancer subtypes and stages can be exploited for disease stratification and risk assessment [5]. Furthermore, circulating ncRNAs present in body fluids, such as blood and saliva, hold potential as minimally invasive biomarkers for early detection and monitoring of breast cancer progression. Integrating ncRNA signatures into multi-gene panels or liquid biopsy assays may improve the accuracy of breast cancer diagnosis and prognosis, enabling personalized treatment strategies [6].

Therapeutic Targeting of Non-Coding RNAs: ncRNAs represent attractive targets for therapeutic intervention in breast cancer. Strategies for modulating ncRNA activity include antisense oligonucleotides (ASOs), small molecule inhibitors and gene editing technologies. ASOs designed to target oncogenic miRNAs or up regulate tumor-suppressive miRNAs have shown promise in preclinical models of breast cancer, inhibiting tumor growth and metastasis [7]. Moreover, targeting dysregulated lncRNAs or circRNAs implicated in breast cancer pathogenesis holds potential for developing novel therapeutic approaches. However, challenges such as delivery efficiency, off-target effects, and systemic toxicity must be overcome to translate ncRNA-targeted therapies into clinical practice.

Applications: Biomarker discovery: Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), can serve as diagnostic, prognostic, and predictive biomarkers for breast cancer, aiding in early detection, risk stratification, and treatment decision-making [8].

Pathway regulation: ncRNAs play crucial roles in regulating key signaling pathways involved in breast cancer pathogenesis, including cell proliferation, apoptosis, invasion, metastasis, and angiogenesis, offering potential targets for therapeutic intervention.

Tumor suppression: Certain ncRNAs act as tumor suppressors by negatively regulating oncogenic pathways or promoting the expression of tumor-suppressive genes, thereby inhibiting breast cancer development and progression [9].

Oncogene activation: Conversely, dysregulated expression of specific ncRNAs can activate oncogenes or inhibit tumor suppressors, contributing to aberrant cellular behaviors associated with breast cancer, such as uncontrolled proliferation, evasion of apoptosis, and metastatic dissemination.

Epigenetic regulation: ncRNAs participate in epigenetic regulation by modulating DNA methylation, histone modifications, and chromatin remodeling, influencing gene expression patterns in breast cancer cells and altering their phenotypic characteristics and therapeutic responses.

Drug resistance: ncRNAs have been implicated in the development of drug resistance in breast cancer cells by modulating drug efflux mechanisms, promoting cell survival pathways, and inducing epithelial-mesenchymal transition (EMT), highlighting their potential as therapeutic targets to overcome resistance.

Metastasis promotion: ncRNAs regulate various steps of the metastatic cascade in breast cancer, including invasion into surrounding tissues, intravasation into blood or lymphatic vessels, survival in the circulation, extravasation at distant sites, and colonization of secondary organs, making them attractive targets for anti-metastatic therapies [10].

Immune regulation: ncRNAs modulate immune responses in the breast tumor microenvironment by regulating the expression of immune checkpoint molecules, cytokines, chemokines, and other immune-related genes, influencing tumor-immune interactions and shaping the anti-tumor immune response.

Therapeutic targeting: ncRNAs represent promising therapeutic targets for breast cancer treatment, with various strategies under investigation, including antisense oligonucleotides, small interfering RNAs (siRNAs), antagomirs, small molecule inhibitors, and CRISPR-based gene editing approaches.

Clinical translation: Translational research efforts are focused on validating the diagnostic, prognostic, and therapeutic potential of ncRNAs in breast cancer through preclinical models, clinical trials, and biomarker validation studies, with the ultimate goal of improving patient outcomes and quality of life.

Discussion

The dysregulation of ncRNAs in breast cancer underscores their intricate involvement in disease pathogenesis and highlights their potential as diagnostic markers and therapeutic targets. However, several challenges and considerations must be addressed to realize the full clinical potential of ncRNAs. Standardization of detection methods and validation in large, diverse patient cohorts are essential for the development of robust ncRNA biomarkers. Moreover, the development of effective delivery systems and the mitigation of off-target effects are critical for the translation of ncRNA-targeted therapies into clinical practice. Collaborative efforts between researchers, clinicians, and industry stakeholders are essential for advancing our understanding of ncRNA biology and harnessing its therapeutic potential in breast cancer management.

Conclusion

Non-coding RNAs play a crucial role in breast cancer pathogenesis, influencing tumor initiation, progression, and therapeutic response. Understanding the complex regulatory networks orchestrated by ncRNAs offers insights into breast cancer biology and holds promise for developing innovative diagnostic and therapeutic strategies. Integrating ncRNA signatures into clinical practice may improve disease stratification, prognostication, and treatment selection, ultimately improving outcomes for breast cancer patients. Further research into the functional roles of ncRNAs and the development of targeted ncRNA-based therapies are needed to realize the full potential of ncRNA modulation in breast cancer management.

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