New insights of miRNA molecular mechanisms in breast cancer brain metastasis and therapeutic targets

Bashdar Mahmud Hussen; Khozga Hazhar Abdullah; Snur Rasool Abdullah; Nasik Mahmood Majeed; Sayran Mohamadtahr; Mohammed Fatih Rasul; Peixin Dong; Mohammad Taheri; Majid Samsami

doi:10.1016/j.ncrna.2023.09.003

New insights of miRNA molecular mechanisms in breast cancer brain metastasis and therapeutic targets

Noncoding RNA Res. 2023 Sep 28;8(4):645-660. doi: 10.1016/j.ncrna.2023.09.003. eCollection 2023 Dec.

Authors

Affiliations

¹ Department of Biomedical Sciences, College of Science, Cihan University-Erbil, Kurdistan Region, 44001, Iraq.
² Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Kurdistan Region, Erbil, Iraq.
³ Medical Laboratory Science, College of Health Sciences, Lebanese French University, Kurdistan Region, Erbil, Iraq.
⁴ Maternity Hospital-Erbil, Breast Center, Kurdistan Region, Erbil, Iraq.
⁵ Department of Pharmacology and Toxicology, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
⁶ Department of Pharmaceutical Basic Science, Tishk International University, Erbil, Kurdistan Region, Iraq.
⁷ Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan.
⁸ Institute of Human Genetics, Jena University Hospital, Jena, Germany.
⁹ Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
¹⁰ Cancer Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Brain metastases in breast cancer (BC) patients are often associated with a poor prognosis. Recent studies have uncovered the critical roles of miRNAs in the initiation and progression of BC brain metastasis, highlighting the disease's underlying molecular pathways. miRNA-181c, miRNA-10b, and miRNA-21, for example, are all overexpressed in BC patients. It has been shown that these three miRNAs help tumors grow and metastasize by targeting genes that control how cells work. On the other hand, miRNA-26b5p, miRNA-7, and miRNA-1013p are all downregulated in BC brain metastasis patients. They act as tumor suppressors by controlling the expression of genes related to cell adhesion, angiogenesis, and invasion. Therapeutic miRNA targeting has considerable promise in treating BC brain metastases. Several strategies have been proposed to modulate miRNA expression, including miRNA-Mimics, antagomirs, and small molecule inhibitors of miRNA biogenesis. This review discusses the aberrant expression of miRNAs and metastatic pathways that lead to the spread of BC cells to the brain. It also explores miRNA therapeutic target molecular mechanisms and BC brain metastasis challenges with advanced strategies. The targeting of certain miRNAs opens a new door for the development of novel therapeutic approaches for this devastating disease.

Keywords: Biomarker; Brain metastasis; Breast cancer; Therapeutic strategies; microRNAs (miRNAs).