0000000000324997
AUTHOR
Eduardo Tormo
MicroRNA-33b Suppresses Epithelial-Mesenchymal Transition Repressing the MYC-EZH2 Pathway in HER2+ Breast Carcinoma
Downregulation of miR-33b has been documented in many types of cancers and is being involved in proliferation, migration, and epithelial-mesenchymal transition (EMT). Furthermore, the enhancer of zeste homolog 2-gene (EZH2) is a master regulator of controlling the stem cell differentiation and the cell proliferation processes. We aim to evaluate the implication of miR-33b in the EMT pathway in HER2+ breast cancer (BC) and to analyze the role of EZH2 in this process as well as the interaction between them. miR-33b is downregulated in HER2+ BC cells vs healthy controls, where EZH2 has an opposite expression in vitro and in patients' samples. The upregulation of miR-33b suppressed proliferatio…
The role of miR-26a and miR-30b in HER2+ breast cancer trastuzumab resistance and regulation of the CCNE2 gene
AbstractA subset of HER2+ breast cancer patients manifest clinical resistance to trastuzumab. Recently, miR-26a and miR-30b have been identified as trastuzumab response regulators, and their target gene CCNE2 seems to play an important role in resistance to trastuzumab therapy. Cell viability was evaluated in trastuzumab treated HER2+ BT474 wt (sensitive), BT474r (acquired resistance), HCC1954 (innate resistance), and MDA-MB-231 (HER2−) cell lines, and the expression of miR-26a, miR-30b, and their target genes was measured. BT474 wt cell viability decreased by 60% and miR-26a and miR-30b were significantly overexpressed (~3-fold, p = 0.003 and p = 0.002, respectively) after trastuzumab trea…
The role of AXL as mechanism of resistance to trastuzumab and a prognostic factor in breast cancer HER2 positive: A translational approach
Abstract Background Breast cancer (BC) is a heterogeneous disease. HER2+ BC represents between 15-30% of cases. Trastuzumab (T), a monoclonal antibody, has been successfully improved clinical benefits in both adjuvant and in metastatic settings. Despite this evidence, many patients experience resistance to therapy. The objective of this study is to assess AXL as a potential mechanism of resistance and its implication as a prognostic factor. Methods We used three cell lines with acquired resistance to T. Resistant models were generated by treating parental cells (AU565, SKR3, BT474) with constant dose of T (15mg/mL) for 6 months. Cell viability was estimated by MTT assay. Proteins were asses…
MicroRNA Profile in Response to Doxorubicin Treatment in Breast Cancer
UNLABELLED Chemotherapy treatment is the standard in triple negative breast cancers, a cancer subgroup which lacks a specific target. The mechanisms leading to the response, as well as any markers that allow the differentiation between responder and non-responder groups prior to treatment are unknown. In parallel, miRNAs can act as oncogenes or tumor suppressors and there is evidence of their involvement in promoting resistance to anticancer drugs. Therefore we hypothesized that changes in miRNA expression after doxorubicin treatment may also be relevant in treatment response. OBJECTIVE To study miRNAs that are differentially expressed in response to doxorubicin treatment. METHODS One lumin…
BCL2 gene polymorphisms and splicing variants in chronic myeloid leukemia.
Recent data suggest that constitutional genetic variation in the antiapoptotic BCL2 gene could be associated with the susceptibility to develop chronic myeloid leukemia (CML) and the clinical outcome in several hematological malignancies. The present study examines whether BCL2 single nucleotide polymorphisms (SNPs) predispose to CML or may potentially influence the disease characteristics at diagnosis. Notably, no association was observed between the four candidate BCL2 SNPs and the risk of developing CML. Instead, the 4777C>A (rs2279115) and the 5735A>G (rs1801018) SNPs were significantly associated with the disease risk profile as determined by the Sokal score. We found that such polymor…
HDAC5 Inhibitors as a Potential Treatment in Breast Cancer Affecting Very Young Women
Background: Breast cancer in very young women (BCVY) defined as <
miR-503-5p induces doxorubicin resistance in triple-negative breast cancer.
1083 Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer (BC) subtype comprising approximately 15% of BC. Conventional cytotoxic chemotherapies continue to be the mainstay for treatment of this BC, which lacks targetable markers. In this context, microRNAs have been described to have an important role. The aim of this work was to elucidate the function of miR-503-5p in doxorubicin resistance in TNBC. Methods: miR-503-5p expression was evaluated in the TNBC cell line with acquired resistance to doxorubicin (MDA-MB-231R) and its parental cell line (MDA-MB-231), by qRT-PCR. Studies of gain/loss of function of miR-503-5p were carried out in MDA-MB-231 and MDA-MB-231…
Thirteen miRNAs involved in the response of breast cancer cells to doxorubicin.
e12019 Background: Mature microRNAs (miRNAs) are a class of naturally occurring, small non-coding RNA molecules, about 21–25 nucleotides. Growing evidence shows that miRNAs exhibit a variety of regulatory functions related to cell growth, development, and differentiation, and are associated with a wide variety of human diseases. Several miRNAs have been linked to cancer; since expression analysis studies have revealed perturbed miRNA expression in tumors compared to normal tissues. As a consequence, human miRNAs are likely to be highly useful as biomarkers, especially for future cancer diagnostics, and are emerging as targets for disease intervention. Since doxorubicin (DOX) has been used …