No abstract

Breast cancer ranks first in incidence and mortality in working age women. Cancer initiation and progression relies on accumulation of genetic and epigenetic aberrations that alter cellular processes, among them, epithelial to mesenchymal transition (EMT) denotes particularly aggressive neoplasias given its capacity to invade and metastasize. Several microRNAs (miRNA) have been found able to regulate gene expression at the core of EMT. In this study, the Affymetrix CytoScan HD array was used to analyze three different primary tumor cell isolates from Mexican breast cancer patients. We found an amplification in band 22q11.2 shared by the three samples, in the region that encodes miRNA-650. Overexpression of this miRNA has been associated with downregulation of tumor suppressors ING4 and NDRG2, which have been implicated in cancer progression. Using the Pathway Linker platform the ING4 and NDRG2 interaction networks showed a significant association with signaling pathways commonly deregulated in cancer. Also, several studies support their participation in the EMT. Supporting the latter, we found that the three primary isolates were E-cadherin negative, vimentin positive, presented a cancer stem cell-like phenotype CD44+CD24−/low and were invasive in Transwell invasion assays. This evidence suggests that the gain of region 22q11.2 contributes to trigger EMT. This is the first evidence linking miR-650 and breast cancer.

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