The regulation of microRNAs on chemoresistance in triple-negative breast cancer: a recent update
Creators: name: Yan, Li-Jun
name: Lau, Andy T. Y.
name: Xu, Yan-Ming
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biophysics
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Pharmacology
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Plant Biology

description: Triple-negative breast cancer (TNBC) has negative expressions of ER, PR and HER2. Due to the insensitivity to both endocrine therapy and HER2-targeted therapy, the main treatment method for TNBC is cytotoxic chemotherapy. However, the curative effect of chemotherapy is limited because of the existence of acquired or intrinsic multidrug resistance. MicroRNAs (miRNAs) are frequently dysregulated in malignant tumors and involved in tumor occurrence and progression. Interestingly, growing studies show that miRNAs are involved in chemoresistance in TNBC. Thus, targeting dysregulated miRNAs could be a plausible way for better treatment of TNBC. Here, we present the updated knowledge of miRNAs associated with chemoresistance in TNBC, which may be helpful for the early diagnosis, prognosis and treatment of this life-threatening disease. Triple-negative breast cancer (TNBC) is a subtype of breast cancer, which is characterized by high rates of invasion, recurrence and distant metastasis. At present, chemotherapy is still the main treatment option for TNBC. However, after some time, the sensitivity of tumor cells to chemotherapeutic drugs gradually decreases, which makes tumor cells develop chemoresistance. MicroRNAs (miRNAs) are a class of small RNA molecules with length of 19–25 nucleotides that do not encode proteins. The expression level of miRNAs in cancer is usually abnormal. More and more studies have shown that miRNAs are involved in cancer development and associated with drug resistance. Therefore, this review summarizes the miRNAs associated with chemoresistance in TNBC. Review discussing the role of microRNAs in the development of chemoresistance in TNBC to indicate that they could be therapeutic targets and improve the chemosensitivity of TNBC. Triple-negative breast cancer (TNBC) is one breast cancer subtype characterized by lack of PR, ER and HER2 expressions. Due to the absence of ER, PR and HER2, the application of endocrine therapy and anti-HER2-targeted therapy in TNBC is limited. At present, chemotherapy is still the main treatment option for TNBC, but it is easy to produce chemoresistance, which is the main cause of chemotherapy failure. MiRNAs can bind to the 3′-UTR of target mRNAs and then regulate their expression level. As oncogenes or tumor suppressors, miRNAs not only are involved in basic biological processes, including proliferation, migration, invasion and apoptosis, but also play a key role in chemoresistance. Drug transporters can transport anti-cancer drugs out of tumor cells, reducing the accumulation of drugs and causing drug resistance in tumor cells. Some miRNAs could regulate drug efflux and thus participate in chemoresistance of TNBC. The evasion of apoptosis confers chemoresistance to some cytotoxic drugs. MiRNAs could regulate apoptosis-related factors and thus regulate drug resistance in TNBC. Epithelial–mesenchymal transition (EMT) can be regulated by miRNAs and participate in some processes of cancer occurrence and development as well as chemoresistance. Genomic instability (GIN) is the key to tumor development and tumor chemoresistance, among which DNA damage response is a vital biological process to maintain the genome stability. MiRNAs could regulate DNA damage response and thus affect chemoresistance. Some signaling pathways are related to the chemoresistance of tumor cells, such as Wnt/β-catenin, Notch, TGF-β, ERK, and PI3K/AKT/mTOR signaling pathway. MiRNAs regulate the development of drug resistance in TNBC via the participation in modulating various signaling pathways. MiRNAs are associated with most of the mechanisms of chemoresistance in TNBC. No studies show that miRNAs are related to other mechanisms of chemoresistance, such as CSCs induction after NAC, hypoxia and Hedgehog signaling pathway. MiRNAs can regulate their target genes and then participate in drug resistance of TNBC. MiRNAs have the potential therapeutic value in gene therapy strategy. Specific miRNAs are promising to become biomarkers for diagnosis and possible therapeutic targets for TNBC. Controlling the expression level of cancer-associated miRNAs is a novel treatment strategy for TNBC. Clinical trials of miRNA inhibitors or mimics that can treat TNBC or improve drug sensitivity of TNBC may be a future research direction.