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microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy
Ranjana K Kanchan1, Jawed A Siddiqui1, Sidharth Mahapatra1,2
1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Abstract:
Brain metastasis (BM) predominantly occurs in triple-negative (TN) and epidermal growth factor 2 (HER2)-positive breast cancer (BC) patients, and currently, there is an unmet need for the treatment of these patients. BM is a complex process that is regulated by the formation of a metastatic niche. A better understanding of the brain metastatic processes and the crosstalk between cancer cells and brain microenvironment is essential for designing a novel therapeutic approach. In this context, the aberrant expression of miRNA has been shown to be associated with BM. These non-coding RNAs/miRNAs regulate metastasis through modulating the formation of a metastatic niche and metabolic reprogramming via regulation of their target genes. However, the role of miRNA in breast cancer brain metastasis (BCBM) is poorly explored. Thus, identification and understanding of miRNAs in the pathobiology of BCBM may identify a novel candidate miRNA for the early diagnosis and prevention of this devastating process. In this review, we focus on understanding the role of candidate miRNAs in the regulation of BC brain metastatic processes as well as designing novel miRNA-based therapeutic strategies for BCBM.
Insights
MicroRNAs (miRNAs) are key regulators in breast cancer brain metastasis (BCBM). Understanding their role in forming metastatic niches and metabolic reprogramming is crucial for developing new treatments.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Brain metastasis (BM) is a significant challenge in triple-negative (TN) and HER2-positive breast cancer (BC), with limited treatment options.
- BM involves complex interactions within a metastatic niche, requiring a deeper understanding of cancer cell and brain microenvironment crosstalk.
- Aberrant microRNA (miRNA) expression is linked to metastasis, influencing niche formation and metabolic reprogramming.
Purpose of the Study:
- To explore the role of miRNAs in the pathobiology of breast cancer brain metastasis (BCBM).
- To identify novel candidate miRNAs for early diagnosis and prevention of BCBM.
- To review current understanding and propose miRNA-based therapeutic strategies for BCBM.
Main Methods:
- Literature review focusing on the function of specific miRNAs in BCBM.
- Analysis of miRNA-mediated regulation of metastatic niche formation.
- Investigation of miRNA's role in metabolic reprogramming during brain metastasis.
Main Results:
- miRNAs are implicated in regulating the formation of the brain metastatic niche.
- miRNAs modulate metabolic reprogramming in cancer cells contributing to BCBM.
- The specific roles of many miRNAs in BCBM remain underexplored.
Conclusions:
- Understanding miRNA involvement in BCBM is essential for developing targeted therapies.
- Candidate miRNAs may serve as biomarkers for early BCBM diagnosis and prevention.
- miRNA-based strategies hold promise for novel therapeutic approaches to BCBM.
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