Circulating microRNAs and their role in the immune response in triple‑negative breast cancer (Review)

Abstract

Breast cancer (BC) is the most common type of cancer in women worldwide, and despite advances in treatments, its incidence and mortality are increasing. Therefore, it is necessary to develop new, non-invasive tests that provide more accurate diagnosis and prognosis in a timely manner. A promising approach is measuring the presence of biomarkers to detect tumors at various stages and determine their specific characteristics, thus allowing for more personalized treatment. MicroRNAs (miRNAs) serve a role in gene expression, primarily by interacting with messenger RNAs, and may be potential biomarkers for detecting cancer. They are detectable in tissues and blood, including plasma and/or serum, are stable and often tumor specific. Also, different miRNAs are associated with specific BC molecular subtypes. Triple-negative BC (TNBC) is a type of BC in which the primary targets for hormonal therapy are absent. It is an aggressive phenotype, which frequently metastasizes and is associated with an unfavorable prognosis. The present review focuses on circulating miRNAs in patients with TNBC, with an emphasis on their interaction with the immune response checkpoint genes PD-1, PD-L1 and CTLA4. Modulation and response of the immune system are of interest in cancer treatment due to the success of immunotherapy in the treatment of various neoplasms. Based on the findings of this literature review and the in silico analysis performed as part of this review, it is concluded that circulating hsa-miR-195 and hsa-miR-155 in TNBC interact with checkpoint genes involved in the immune response. Further analysis of the expression of these circulating miRNAs and their association with prognosis in patients with TNBC treated with immunotherapy should be assessed to evaluate their possible use as non-invasive predictive biomarkers. In addition, functional studies to analyze biologically relevant targets in the development and prognosis of TNBC, which could be therapeutic targets, are also recommended. Contents 1. Introduction 2. miRNAs as biomarkers in BC 3. Circulating miRNAs in BC 4. Checkpoints and miRNAs in TNBC 5. Conclusions

Research advances and new challenges in overcoming triple-negative breast cancer

“…This study provides a new perspective on cancer surveillance and treatment response evaluation in cancer patients treated with immunotherapy. Finally, noncoding RNAs, including microRNA (miRNA) and long-noncoding RNA (lncRNA), are considered as novel sources of prognostic and predictive biomarkers in TNBC and have been evaluated in both tissue specimens and as circulating miRNAs [139] . Certain circulating miRNAs were reported to be interacting with checkpoint genes involved in the immune response, which could be assessed in TNBC patients treated with immunotherapy as response predictive factors [140] .…”

“…Finally, noncoding RNAs, including microRNA (miRNA) and long-noncoding RNA (lncRNA), are considered as novel sources of prognostic and predictive biomarkers in TNBC and have been evaluated in both tissue specimens and as circulating miRNAs [ 139 ] . Certain circulating miRNAs were reported to be interacting with checkpoint genes involved in the immune response, which could be assessed in TNBC patients treated with immunotherapy as response predictive factors [ 140 ] . Moreover, subtypes based on immune-functional lncRNA signatures were shown to have strong prognostic value in bladder cancer and melanoma patients receiving immunotherapy [ 141 ] .…”

Cancer Biology, Epidemiology, and Treatment in the 21st Century: Current Status and Future Challenges From a Biomedical Perspective

“…Likewise, the horizon expands for therapeutic alternatives in oncology with the use of epidrugs, such as pharmacoepigenomic modulators for genes and key pathways, including methylation of promoters and regulation of micro-RNAs involved in chemoresponse and immune response in cancer. 39 There is no doubt that integrated approaches identifying stable pharmagenomic and epigenomic patterns and their relation with expression profiles and genetic functions will be more and more valuable in our fight against cancer.…”

Novel miRNA Targets and Therapies in the Triple-Negative Breast Cancer Microenvironment: An Emerging Hope for a Challenging Disease

“…PD-L1 expression, which mediates immune evasion, is a direct target of miR-195/miR497 in TNBC [ 116 ]. Circulating miR-195-5p, which is up-regulated in TNBC [ 117 ], has also been identified as a candidate regulator of PD1 in TNBC [ 118 ]. Another circulating miRNA in TNBC, miR-155 [ 119 ], is known to regulate the immune checkpoint receptor CTLA4 [ 118 ].…”

“…EMT and ECM targets inhibits EMT, proliferation, invasion [107] miR-148a Wnt-1 inhibits Wnt signaling [50] miR-340 Rock1, cMyc, CTNNB1 inhibits Wnt signaling [48] miR-137 FSTL1 Wnt signaling [51] miR-4417 multiple Inhibits mammosphere formation [108] miR-142-3p HIF1α, LOX stromal stiffness, drug exclusion [86] Fibroblasts/CAFs ER-regulated miRNAs multiple proliferation, migration, apoptosis, angiogenesis [7] miR-320 ETS2 inhibits MMP secretion, angiogenesis [113] miR-205 VEGF-A, ZEB1, YAP1 angiogenesis [114] miR-9 E-cadherin activation [131] miR-125b TP53inp1 activation [132] miR-222 LBR activation, migration [115] Immune Infiltrates miR-34a IL-6R macrophage polarization [73] mir-195/miR-497 PD-L1 immune checkpoint [116] miR-195-5p PD1 immune checkpoint [118] miR-155 CTLA4 immune checkpoint [118,119]…”