• breast cancer
• metastasis
• miR‐200c
• microRNA
• migration

• MicroRNAs/genetics
• MicroRNAs/metabolism
• Animals
• Humans
• Female
• Breast Neoplasms/pathology
• Breast Neoplasms/genetics
• Cell Movement/genetics
• Neoplasm Metastasis/genetics
• Mice
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• MCF-7 Cells

• 201269156 Collaborative Research Center SFB 1032 Deutsche Forschungsgemeinschaft
• Deutsche Forschungsgemeinschaft

• Breast cancer
• Cancer chemoresistance
• EMT
• Metastasis
• ZEB

• Humans
• Drug Resistance, Neoplasm
• Breast Neoplasms/pathology
• Breast Neoplasms/metabolism
• Female
• Zinc Finger E-box-Binding Homeobox 1/metabolism
• Zinc Finger E-box Binding Homeobox 2/metabolism
• Zinc Finger E-box Binding Homeobox 2/genetics
• Tumor Microenvironment
• Neoplasm Metastasis

• CircRNA
• EMT
• LncRNA
• MiR-200
• MiRNA
• TGF-β

• Epithelial-Mesenchymal Transition/genetics
• Humans
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/metabolism
• Transforming Growth Factor beta/metabolism
• Transforming Growth Factor beta/genetics
• Signal Transduction
• Animals
• Gene Expression Regulation, Neoplastic
• MicroRNAs/genetics
• RNA, Long Noncoding/genetics
• RNA, Circular/genetics

• Corneal damage
• EMT
• Inflammation
• Neovascularization
• Scarring
• ZEB1

• 8217032 National Natural Science Foundation of China
• 2022JH2/101300036 Liaoning Provincial Applied Basic Research Project
• 20180550976 Natural Science Foundation of Liaoning Province
• 201800209 Natural Science Foundation of Liaoning Province
• 2020-MS-399 Natural Science Foundation of Liaoning Province
• 2023JJ12034 Dalian Science and Technology Innovation Fund
• 2021RQO33 Youth Science and Technology Star Project of Dalian
• 2111008 Health and Family Planning Commission of Sichuan Province
• EY024110 National Institute of Health
• P20GM103453 National Institute of Health
• MTEC-22-02-MPAI-005 U.S. Department of Defense

• Humans
• ST Elevation Myocardial Infarction/diagnostic imaging
• ST Elevation Myocardial Infarction/genetics
• ST Elevation Myocardial Infarction/therapy
• Percutaneous Coronary Intervention/methods
• Anterior Wall Myocardial Infarction/complications
• MicroRNAs/genetics
• Biomarkers
• Endothelial Cells
• Treatment Outcome

• CH/16/1/32013 British Heart Foundation
• CH/16/3/32406 British Heart Foundation
• RG/F/22/110085 British Heart Foundation

• DCIS.
• Next Generation sequencing
• benign tumor
• breast cancer
• ceRNA
• small RNAs

• Humans
• Female
• MicroRNAs/genetics
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Breast Neoplasms/mortality
• Gene Expression Regulation, Neoplastic/genetics
• Carcinoma, Intraductal, Noninfiltrating/genetics
• Carcinoma, Intraductal, Noninfiltrating/pathology
• Carcinoma, Ductal, Breast/genetics
• Carcinoma, Ductal, Breast/pathology
• Middle Aged
• Neoplasm Staging
• Gene Expression Profiling
• Biomarkers, Tumor/genetics
• Transcriptome/genetics

• BT/PR8152/AGR/36/739/2013 Department of Biotechnology, Govt. of India

• breast cancer
• tumour-suppressor proteins
• oncogenes
• ubiquitylation
• ubiquitin ligases

• Humans
• Cell Transformation, Neoplastic
• F-Box Proteins/genetics
• Microfilament Proteins
• Oncogenes
• Proto-Oncogene Proteins c-akt
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology

• TBK1
• broad-spectrum
• influenza virus
• innate immunity
• interferon
• microRNA-200b-3p
• viral infection

• Humans
• Animals
• Mice
• NF-kappa B/metabolism
• 3' Untranslated Regions
• MicroRNAs/metabolism
• Virus Diseases/genetics
• Interferon Type I/genetics
• Interferon Type I/metabolism
• Antiviral Agents/pharmacology
• Virus Replication
• Protein Serine-Threonine Kinases/genetics

• MOST | National Key Research and Development Program of China (NKPs)

• Fibronectin-1
• Magnolia bark
• Xenograft
• α-SMA
• β-catenin

• Animals
• Mice
• Humans
• Male
• Epithelial-Mesenchymal Transition/genetics
• Retinoblastoma/drug therapy
• Retinoblastoma/genetics
• Cell Line, Tumor
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Cadherins/metabolism
• Retinal Neoplasms/genetics
• Gene Expression Regulation, Neoplastic
• Cell Movement/genetics
• Zinc Finger E-box-Binding Homeobox 1/genetics
• Zinc Finger E-box-Binding Homeobox 1/metabolism

• Adipose tissue
• Breast cancer
• Inflammation
• Metabolism
• Obesity
• Treatment

• colon cancer
• metastasis
• bioinformatics
• cancer genomics

• Colorectal Neoplasms/pathology
• Humans
• Neoplasms, Second Primary
• Peritoneal Neoplasms/genetics
• Peritoneal Neoplasms/secondary
• Peritoneum/metabolism
• Quality of Life

• KWF Kankerbestrijding (Dutch Cancer Society)
• ZonMw (Netherlands Organisation for Health Research and Development)
• This work is supported by the Academic Medical Center (Amsterdam), The New York Stem Cell Foundation, L.V. is a New York Stem Cell Foundation – Robertson Investigator.

MiR-21 was identified as a gene whose expression correlated with the extent of metastasis of murine mammary tumours. Since miR-21 is recognised as being associated with poor prognosis in cancer, we investigated its contribution to mammary tumour growth and metastasis in tumours with capacity for spontaneous metastasis. Unexpectedly, we found that suppression of miR-21 activity in highly metastatic tumours resulted in regression of primary tumour growth in immunocompetent mice but did not impede growth in immunocompromised mice. Analysis of the immune infiltrate of the primary tumours at the time when the tumours started to regress revealed an influx of both CD4⁺ and CD8⁺ activated T cells and a reduction in PD-L1⁺ infiltrating monocytes, providing an explanation for the observed tumour regression. Loss of anti-tumour immune suppression caused by decreased miR-21 activity was confirmed by transcriptomic analysis of primary tumours. This analysis also revealed reduced expression of genes associated with cell cycle progression upon loss of miR-21 activity. A second activity of miR-21 was the promotion of metastasis as shown by the loss of metastatic capacity of miR-21 knockdown tumours established in immunocompromised mice, despite no impact on primary tumour growth. A proteomic analysis of tumour cells with altered miR-21 activity revealed deregulation of proteins known to be associated with tumour progression. The development of therapies targeting miR-21, possibly via targeted delivery to tumour cells, could be an effective therapy to combat primary tumour growth and suppress the development of metastatic disease.

• Animals
• Embryonic Development/genetics
• Fibrosis
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasms/genetics
• Neurodegenerative Diseases/genetics

Exportin 5 (XPO5) is a shuttle protein that mediates precursor miRNA (pre‐miRNA) export from the nucleus to the cytoplasm, an important step in miRNA maturation. We previously demonstrated that XPO5 was phosphorylated by ERK kinase and subsequently underwent conformation change by the peptidyl‐prolyl isomerase Pin1, leading to the reduced miRNA expression in hepatocellular carcinoma (HCC). Protein phosphorylation modification serves as a reversible regulatory mechanism precisely governed by protein kinases and phosphatases. Here we identified that the phosphatase PP2A catalyzed XPO5 dephosphorylation. PP2A holoenzyme is a ternary complex composed of a catalytic subunit, a scaffold subunit, and a regulatory subunit that determines substrate specificity. In this study, we characterized the involvement of B55β subunit in XPO5 dephosphorylation that favored the distribution of XPO5 into the cytoplasm and promoted miRNA expression, leading to HCC inhibition in vitro and in vivo. Our study demonstrates the regulatory role of B55β‐containing PP2A in miRNA expression and may shed light on HCC pathogenesis.

Breast cancer cells with mesenchymal characteristics, particularly the claudin-low subtype, express extremely low levels of miR-200s. Therefore, this study examined the functional impact of restoring miR-200 expression in a human claudin-low breast cancer cell line MDA-MB-231. MDA-MB-231 cells were stably transfected with a control vector (MDA-231EV) or the miR-200c/141 cluster (MDA-231c141). Injection of MDA-231c141 cells into the 4th mammary gland of NCG mice produced tumors that developed significantly slower than tumors produced by MDA-231EV cells. Spontaneous metastasis to the lungs was also significantly reduced in MDA-231c141 cells compared to MDA-231EV cells. RNA sequencing of MDA-231EV and MDA-231c141 tumors identified genes including MXRA8 as being downregulated in the MDA-231c141 tumors. MXRA8 was further investigated as elevated levels of MXRA8 were associated with reduced distant metastasis free survival in breast cancer patients. Quantitative RT-PCR and Western blotting confirmed that MXRA8 expression was significantly higher in mammary tumors induced by MDA-231EV cells compared to those induced by MDA-231c141 cells. In addition, MXRA8 protein was present at high levels in metastatic tumor cells found in the lungs. This is the first study to implicate MXRA8 in human breast cancer, and our data suggests that miR-200s inhibit growth and metastasis of claudin-low mammary tumor cells in vivo through downregulating MXRA8 expression.

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury.

• apoptosis
• exosomes
• ionizing radiation
• miRNome
• neonatal cerebellum
• proteomics

• Animals
• Apoptosis
• Cerebellum/metabolism
• Exosomes/metabolism
• Mammals/metabolism
• Mice
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Proteomics
• Radiation Injuries/metabolism

• Cytokine receptors(4)
• Immune checkpoint(3)
• Immunotherapy(1)
• Tumor immunology(5)
• regulatory T cell(2)

• MSN
• breast cancer
• lymph node metastasis
• meta-analysis
• prognosis

• National Natural Science Foundation of China

• Immune lymphocytes
• Infiltration
• Inflammation
• Lung adenocarcinoma
• Moesin
• Poor prognosis

• bladder cancer
• meta-analysis
• mir-200 family
• prognosis

• Biomarkers, Tumor/genetics
• Humans
• MicroRNAs/genetics
• Prognosis
• Urinary Bladder Neoplasms/genetics

• Breast cancer
• MicroRNA
• Pathogenesis
• Therapy

Triple-negative breast cancer (TNBC) refers to breast cancer that does not have receptors for estrogen, progesterone, and HER2 protein. TNBC accounts for 10–20% of all cases of breast cancers and is characterized by its metastatic aggressiveness, poor prognosis, and limited treatment options. Here, we show that the metastatic nature of TNBC is critically regulated by a functional link between miR-200a and the transcription factor ELK3. We found that the expression levels of miR-200a and the ELK3 mRNA were negatively correlated in the luminal and TNBC subtypes of breast cancer cells. In vitro experiments revealed that miR-200a directly targets the 3’ untranslated region (UTR) of the ELK3 mRNA to destabilize the transcripts. Furthermore, ectopic expression of miR-200a impaired the migration and invasion of TNBC cells by reducing the expression level of the ELK3 mRNA. In in vivo studies, transfection of MDA-MB 231 cells (a claudin-low TNBC cell type) with exogenous miR-200a reduced their extravasation into the lung during 48 h after tail vein injection, and co-transfection of the cells with an expression plasmid harboring ELK3 that lacked an intact 3’UTR recovered their extravasation ability. Overall, our findings provide evidences that miR-200a and ELK3 is functionally linked to regulate invasive characteristics of breast cancers.

• 3’ untranslated region (UTR)
• ELK3
• breast cancer
• cell migration and invasion
• extravasation
• miR-200a
• post-transcriptional modification

• Biomarkers
• Blood
• Breast cancer
• Cell-free miRNA
• Diagnosis
• Plasma

• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Breast Neoplasms/blood
• Breast Neoplasms/diagnosis
• Breast Neoplasms/pathology
• Early Detection of Cancer/methods
• Female
• Humans
• MicroRNAs/blood
• MicroRNAs/genetics
• Prognosis
• RNA, Neoplasm/blood
• RNA, Neoplasm/genetics

• H3K27ac/acetylation
• ce-RNA
• imprinting
• linc-RNA
• lnc-RNA
• metastasis
• methylation
• miRNA

• Metastasis
• Self-Renewal
• Spheroid
• miR-200c
• miR-30c

• colorectal
• depth of tumor invasion
• distant metastasis
• lymph node
• mirnas
• qrt-pcr

• Adenocarcinoma/chemistry
• Adenocarcinoma/diagnosis
• Adenocarcinoma/genetics
• Aged
• Aged, 80 and over
• Colorectal Neoplasms/chemistry
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• MicroRNAs/analysis
• MicroRNAs/genetics
• Middle Aged
• Romania

Breast cancer (BrC) is the most frequent malignancy and the leading cause of cancer death among women worldwide. Approximately 70% of BrC are classified as luminal-like subtype, expressing the estrogen receptor. One of the most common and effective adjuvant therapies for this BrC subtype is endocrine therapy. However, its effectiveness is limited, with relapse occurring in up to 40% of patients. Because microRNAs have been associated with several mechanisms underlying endocrine resistance and sensitivity, they may serve as predictive and/or prognostic biomarkers in this setting. Hence, the main goal of this study was to investigate whether miRNAs deregulated in endocrine-resistant BrC may be clinically relevant as prognostic and predictive biomarkers in patients treated with adjuvant endocrine therapy. A global expression assay allowed for the identification of microRNAs differentially expressed between luminal BrC patients with or without recurrence after endocrine adjuvant therapy. Then, six microRNAs were chosen for validation using quantitative reverse transcription polymerase chain reaction in a larger set of tissue samples. Thus, miR-30c-5p, miR-30b-5p, miR-182-5p, and miR-200b-3p were found to be independent predictors of clinical benefit from endocrine therapy. Moreover, miR-182-5p and miR-200b-3p displayed independent prognostic value for disease recurrence in luminal BrC patients after endocrine therapy. Our results indicate that selected miRNAs’ panels may constitute clinically useful ancillary tools for management of luminal BrC patients. Nevertheless, additional validation, ideally in a multicentric setting, is required to confirm our findings.

• Breast cancer
• biomarkers
• endocrine resistance
• endocrine therapy
• luminal subtype
• microRNAs

Cancer is a genetic and epigenetic disease that involves inactivation of tumor suppressor genes and activation of proto-oncogenes. All-trans retinoic acid (ATRA) is an isomer of retinoic acid involved in the onset of differentiation and apoptosis of a number of normal and cancer cells, functioning as an anti-cancer agent in several neoplasms. Ectopic changes in the expression of certain microRNAs (miRNAs) occur in response to ATRA, leading to phenotypic alterations in neoplastic cell lines. Moreover, the modulation of miRNA patterns upon ATRA-treatment may represent an effective chemopreventive and anti-cancer therapy strategy. The present systematic review was performed to provide an overview of the modulation of ATRA-induced miRNA expression in different types of neoplastic cells and identify the efficacy of intervention factors (i.e., concentration and duration of treatment) and how they influence expression profiles of oncogenesis-targeting miRNAs.

A systematic search was conducted according to the PRISMA statement via the US National Library of Medicine MEDLINE/PubMed bibliographic search engine.

The search identified 31 experimental studies involving human cell lines from nine different cancer types (neuroblastoma, acute myeloid leukemia, breast cancer, lung cancer, pancreatic cancer, glioma, glioblastoma, embryonal carcinoma, and colorectal cancer) treated with ATRA at concentrations ranging from 10^− 3 μmol/L to 10² μmol mol/L for 24 h to 21 days.

The concentrations used and the duration of treatment of cancer cells with ATRA varied widely. The presence of ATRA in the culture medium of cancer cells was able to modulate the expression of more than 300 miRNAs, and inhibit invasive behavior and deregulated growth of cancer cells, resulting in total tumor remission in some cases. ATRA may thus be broadly effective for neoplasm treatment and prevention, although these studies may not accurately represent in vivo conditions. Additional studies are required to elucidate ATRA-induced miRNA modulation during neoplasm treatment.

• All-trans retinoic acid
• Cancer
• Expression modulation
• miRNA

Peritoneal fibrosis and loss of transport function is a common complication contributing to adverse outcomes in patients on long-term peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) in mesothelial cells is a salient feature, but its triggering mechanisms remain obscure. Dysregulation of microRNA (miR) expression is implicated in EMT and tissue fibrosis. We investigated the role of miR-200c in EMT and fibrogenesis in a murine PD model and in cultured peritoneal mesothelial cells. PD-fluid-treated mice showed peritoneal miR-200c expression reduced by 76.2% compared with PBS-treated mice, and this was accompanied by increased peritoneal α-smooth muscle actin, fibronectin, and collagen expression. PD fluid and TGF-β1 both reduced miR-200c expression in cultured mesothelial cells, accompanied by downregulation of E-cadherin and decorin, and induction of fibronectin, collagen I and III, and transcription factors related to EMT. Decorin prevented the suppression of miR-200c by TGF-β1. Lentivirus-mediated miR-200c overexpression prevented the induction of fibronectin, collagen I, and collagen III by TGF-β1, independent of decorin, and partially prevented E-cadherin suppression by TGF-β1. Target genes of miR-200c were identified as ZEB2 and Notch1. Our data demonstrate that miR-200c regulates EMT and fibrogenesis in mesothelial cells, and loss of peritoneal miR-200c contributes to PD-associated peritoneal fibrosis.

• EMT
• TGF-β1
• fibrosis
• mesothelial cells
• miR-200c

• Aged
• Case-Control Studies
• Colorectal Neoplasms/genetics
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Male
• MicroRNAs/genetics
• Middle Aged
• Multivariate Analysis
• Polymorphism, Single Nucleotide
• Survival Analysis

• HI18C19990200 Ministry of Health and Welfare of Korea
• HI15C1972010015 Ministry of Health and Welfare of Korea
• 2018R1D1A1B07047604 National Research Foundation of Korea

MicroRNAs (miRNAs) play an essential role in the initiation, progression and metastasis of breast cancer. It has been confirmed that miR-30b is involved in various cancers. However, the specific involvement of miR-30b on breast cancer metastasis remains unknown. In the current study, we aimed to investigate the role of miR-30b in the progression and metastasis of breast cancer in vitro.

We up-regulated the expression of miR-30b in breast cancer cell lines SKBR3 and MDA-MB-231 by transfecting pCMV-miR-30b vector. CCK8, colony formation, Transwell, and flow cytometry assays were used to examine cell proliferation, migration, invasion and apoptosis, respectively. A dual-luciferase reporter assay was performed to identify the relationship between miR-30b and the target gene. Western blot assay was used to detect related proteins.

Our data showed that the overexpression of miR-30b significantly inhibited proliferation, migration and invasion abilities in SKBR3 and MDA-MB-231 cells. Meanwhile, overexpression of miR-30b induced cell apoptosis for both SKBR3 and MDA-MB-231 cells by regulating the expression of apoptosis-related proteins (Bcl-2, Bax, active Caspase-3, and Caspase-9). Moreover, miR-30b inhibited the activation of the PI3K/Akt signaling pathway by decreasing the phosphorylation levels of Akt and mTOR. Furthermore, we determined that miR-30b could down-regulate the expression of Derlin-1 in a post-transcriptional manner by employing the dual-luciferase reporter and western blot assays. Further analysis demonstrated that depletion of Derlin-1 inhibited Akt phosphorylation, and Derlin-1 could restore the effect of miR-30b on Akt. In addition, the CCK8 assay showed that Derlin-1 could partly reverse the inhibition of cell proliferation of SKBR3 and MDA-MB-231 cells mediated by miR-30b.

Our data demonstrated that miR-30b suppresses the progression and metastasis of breast cancer via inhibition of the PI3K/Akt signaling pathway by targeting Derlin-1 in vitro. This suggests that miR-30b might be a novel potent target for breast cancer therapy.

• Derlin-1
• PI3K/Akt
• breast cancer
• miR-30b
• progression

Several evidences support the idea that a small population of tumour cells representing self‐renewal potential are involved in initiation, maintenance, metastasis, and outcomes of cancer therapy. Elucidation of microRNAs/genes regulatory networks activated in cancer stem cells (CSCs) is necessary for the identification of new targets for cancer therapy. The aim of the present study was to predict the miRNAs pattern, which can target both metastasis and self‐renewal pathways using integration of literature and data mining. For this purpose, mammospheres derived from MCF‐7, MDA‐MB231, and MDA‐MB468 were used as breast CSCs model. They had higher migration, invasion, and colony formation potential, with increasing in stemness‐ and EMT‐related genes expression. Our results determined that miR‐204, ‐200c, ‐34a, and ‐10b contemporarily could target both self‐renewal and EMT pathways. This core regulatory of miRNAs could increase the survival rate of breast invasive carcinoma via up‐regulation of OCT4, SOX2, KLF4, c‐MYC, NOTCH1, SNAI1, ZEB1, and CDH2 and down‐regulation of CDH1. The majority of those target genes were involved in the regulation of pluripotency, MAPK, WNT, Hedgehog, p53, and transforming growth factor β pathways. Hence, this study provides novel insights for targeting core regulatory of miRNAs in breast CSCs to target both self‐renewal and metastasis potential and eradication of breast cancer.

• EMT
• breast cancer stem cell
• metastasis
• miRNAs
• self-renewal

The present study aimed to identify the therapeutic role of the forkhead box M1 (FOXM1)-associated pathway in triple-negative breast cancer (TNBC). Using a Cancer Landscapes-based analysis, a gene regulatory network model was constructed. The present results demonstrated that FOXM1 occupies a key position in gene networks and is a critical regulatory gene in breast cancer. Using breast carcinoma gene expression data from The Cancer Genome Atlas, it was identified that FOXM1 expression was increased in the basal-like breast cancer subtype compared with other breast cancer subtypes. RNA-sequencing analysis of MDA-MB-231 cells treated with 4 and 10 µl/ml Thiostrepton identified 662 and 5,888 significantly differentially expressed genes, respectively. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses demonstrated that FOXM1 was highly associated with multiple biological processes and was markedly associated with metabolic pathways in TNBC. The use of Search Tool for the Retrieval of Interacting Genes/Proteins provided a critical assessment and integration of protein-protein interactions, and demonstrated the multiple important functions of FOXM1 in TNBC. Real-time cell analysis, reverse transcription-quantitative polymerase chain reaction and immunofluorescence staining were used to assess the anti-tumor activity of Thiostrepton in TNBC cells in vitro. The present results identified that suppression of FOXM1 using Thiostrepton inhibited MDA-MB-231 cell proliferation and the expression of cell cycle-associated genes, including cyclin A2, cyclin B2, checkpoint kinase 1, centrosomal protein 55 and polo like kinase 1. Immunofluorescence staining analysis demonstrated that vimentin, filamentous actin and zinc finger E-box-binding homeobox 1 were all decreased following treatment with Thiostrepton. Furthermore, a BALB/C nude mouse subcutaneous xenograft model was used to verify the function of FOXM1 in vivo. The present results demonstrated that FOXM1 inhibition significantly suppressed MDA-MB-231 cell tumorigenesis in vivo. Overall, the present results suggested that FOXM1 is a key gene that serves important roles in multiple biological processes in TNBC and that it may serve as a novel therapeutic target in TNBC.

• Breast cancer
• CRISPR-Cas9 editing
• Cancer vaccines
• Immunotherapy
• Long noncoding RNAs
• MicroRNAs
• Small molecule inhibitors
• Targeted therapy

• endometrial cavity distortion
• microRNA
• uterine leiomyoma

• Adult
• Endometrium/metabolism
• Endometrium/pathology
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genetic Variation
• Humans
• Leiomyoma/metabolism
• Leiomyoma/pathology
• MicroRNAs/genetics
• Phenotype
• Transcriptome

• Breast cancer
• Epidermal growth factor receptor
• Estrogen receptors
• Extracellular matrix
• MicroRNAs

Breast cancer is one of the most common malignant diseases in women. Triple‐negative breast cancer (TNBC) shows higher aggressiveness and recurrence rates than other subtypes, and there are no effective targets or tailored treatments for TNBC patients. Thus, finding effective prognostic markers for TNBC could help clinicians in their ability to care for their patients. We used tissue microarrays (TMAs) to detect microRNA‐493 (miR‐493) expression in breast cancer samples. A miRCURY LNA detection probe specific for miR‐493 was used in in situ hybridization assays. Staining results were reviewed by two independent pathologists and classified as high or low expression of miR‐493. Kaplan–Meier survival plots and multivariate Cox analysis were carried out to clarify the relationship between miR‐493 and survival. In the Kaplan–Meier analysis, patients with high miR‐493 expression had better disease‐free survival than patients with low miR‐493 expression. After adjusting for common clinicopathological factors in breast cancer, the expression level of miR‐493 was still a significant prognostic factor in breast cancer. Further subtype analysis revealed that miR‐493 expression levels were only significantly prognostic in TNBC patients. These results were validated in the Molecular Taxonomy of Breast Cancer International Consortium database for overall survival. We proved the prognostic role of miR‐493 in TNBC by using one of the largest breast cancer TMAs available and validated it in a large public RNA sequencing database.

• DFS
• breast cancer
• microRNA 493
• prognostic factor
• triple-negative

Alterations to transcriptional regulation are an important factor in breast cancer. Noncoding RNA, such as microRNA (miR), have very influential roles in the transcriptional regulation of genes. Transcriptional regulation can be successfully modeled and analyzed using complex network theory. Particularly, interactions between two distinct classes of biological elements, such as miR and genes, can be approached through the bipartite network formalism. Based on bipartite network properties, it is possible to identify highly influential miRs in the network, such as those that have a large number of connections indicating regulation of a large set of genes. Some miRs in a network are nonredundant, which indicates that they are solely responsible of the regulation of a particular set of genes, which in turn may be associated to a particular biological process. We hypothesize that highly influential, nonredundant miRs, which we call Commodore miRs (Cdre-miRs), have an important role on the control of biological functions through transcriptional networks. In this work, we analyze the regulation of gene expression by miRs in healthy and cancerous breast tissue using bipartite miR-gene networks inferred from the Cancer Genome Atlas (TCGA) expression data. We observe differences in the degree, clustering coefficient and redundancy distributions for miRs and genes in the network, indicating differences in the way that these elements interact with each other. Furthermore, we identify a small set of five Cdre-miRs in the breast cancer network: miR-190b, miR-let7i, miR-292-b, miR-511, and miR-141. The neighborhood of genes controlled by each of these miRs is involved in particular biological functions such as dynein structure-associated processes, immune response, angiogenesis, cytokine activity, and cell motility. We propose that these Cdre-miRs are important control elements of biological functions deregulated in breast cancer.

• DNA methylation
• Epithelial to mesenchymal transition
• Kaiso
• Metastasis
• Prostate cancer

• Dormancy
• Mammary tumors
• Metastasis
• MiR-200 family
• MicroRNA