Effect of boundary angle on aero-optical imaging deviation of the blunt-headed side-window vehicle.

This paper defines the intersection angle between the tangent plane at the boundary of aero-optical flow field and the body axis as the boundary angle and focuses on the influence of the boundary angle on the imaging deviation. This paper shows that the boundary angle of the aero-optical flow field is different at different flight conditions, which means the location of the zero value of imaging deviation is different.  With the increase of the line of sight angle, the imaging deviation decreases first and then increases in the opposite direction.  After the change of flight conditions, the boundary angle decreases with the increase of the compression of the flow field.  The imaging deviation increases if the incident light is on the right side of the normal and decreases in the opposite direction.

MicroRNA-541-3p alters lipoproteins to reduce atherosclerosis by degrading Znf101 and Casz1 transcription factors.

High apoB-containing low-density lipoproteins (LDL) and low apoA1-containing high-density lipoproteins (HDL) are associated with atherosclerosis. In search of a molecular regulator that could simultaneously and reciprocally control both LDL and HDL levels, we screened a microRNA (miR) library using human hepatoma Huh-7 cells. We identified miR-541-3p that both decreases apoB and increases apoA1 expression by inducing mRNA degradation of two different transcription factors, Znf101 and Casz1. Znf101 enhances apoB expression while Casz1 represses apoA1 expression. The hepatic knockdown of orthologous Zfp961 and Casz1 genes in mice altered plasma lipoproteins and reduced atherosclerosis without causing hepatic lipid accumulation, most likely by lowering hepatic triglyceride production, increasing HDL cholesterol efflux capacity, and reducing lipogenesis. Notably, human genetic variants in the MIR541, ZNF101, and CASZ1 loci are significantly associated with plasma lipids and lipoprotein levels. This study identifies miR-541-3p and Znf101/Casz1 as potential therapeutic agent and targets, respectively, to reduce plasma lipoproteins and atherosclerosis without causing liver steatosis.

Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti-PD-1 in head and neck cancer.

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti-programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking. In a phase 2 trial (NCT02296684), we observed that 45% of patients treated with two doses of neoadjuvant pembrolizumab experienced marked pTRs (≥50%). Single-cell analysis of 17,158 CD8+ T cells from 14 tumor biopsies, including 6 matched pre-post neoadjuvant treatment, revealed that responding tumors had clonally expanded putative tumor-specific exhausted CD8+ tumor-infiltrating lymphocytes (TILs) with a tissue-resident memory program, characterized by high cytotoxic potential (CTX+) and ZNF683 expression, within the baseline TME. Pathologic responses after 5 weeks of PD-1 blockade were consistent with activation of preexisting CTX+ZNF683+CD8+ TILs, paralleling loss of viable tumor and associated tumor antigens. Response was associated with high numbers of CD103+PD-1+CD8+ T cells infiltrating pretreatment lesions, whereas revival of nonexhausted persisting clones and clonal replacement were modest. By contrast, nonresponder baseline TME exhibited a relative absence of ZNF683+CTX+ TILs and subsequent accumulation of highly exhausted clones. In HNSCC, revival of preexisting ZNF683+CTX+ TILs is a major mechanism of response in the immediate postneoadjuvant setting.

Characterization of a novel picornavirus prevalent in experimental rabbits (Oryctolagus cuniculus).

Here, using viral metagenomic method a novel picornavirus (named UJS-2019picorna, GenBank accession number OP821762) was discovered in fecal and blood samples of experimental rabbits (Oryctolagus cuniculus). The complete genome size of UJS-2019picorna is 7832 bp excluding the poly(A)-tail, with GC content of 44.00% and a nucleotide composition of 28.0% A, 28.0% U, 21.5% G, and 22.5% C. The viral genome has a typical picornavirus organization pattern from the 5'-3' direction: VPg-5' UTR-(L)-P1, (VP4-VP2-VP3-VP1)-P2, (2 A-2B-2C)-P3, (3 A-3B-3C-3D)-3' UTR-poly(A). The P1 region of UJS-2019picorna is related to Erbovirus with amino acid identity of 37.31%, while the P2 and P3 regions are the closest to Bopivirus with amino acid identity of 35.66%-39.53%. According to the Picornaviridae Study Group guidelines, UJS-2019picorna should be presumed to be a new genus belonging to the Picornaviridae family. Epidemiologic study revealed that this novel picornavirus was prevalent in a cohort of experimental rabbits, with prevalence rate of 23.68% (9/38) in feces and 18.4% (7/38) in blood samples. Further work is required to elucidate whether this virus is pathogenic to rabbits and whether it has influence on studies using rabbits as experimental animal.

Influence of 0°-15° attack angle on aero-optical imaging deviation of a blunt-nose vehicle.

A turbulent flow field is created in a vehicle's head during high-speed flight, and this flow field causes the airborne optical system's receiving target images to be displaced, blurred, and jittered. In this study, we examine the impact of a 0°-15° angle of attack on the aero-optical imaging deviation. With the use of modeling and meshing software, we created a model of a conventional blunt-headed vehicle. Computational fluid dynamics calculations were performed using finite element analysis software; the ray equations were solved iteratively by the Runge-Kutta method. Finally, the imaging deviation data were obtained by using reverse ray tracing and tracing stop criteria. The findings demonstrate that, as the angle of attack increases from 0° to 15°, the thickness of the nonuniform flow field above the vehicle flow field cross-section axis gradually increases. As the density of the nonuniform flow field through which light propagates increases, so does the corresponding refractive index and the aero-optical imaging deviation.

Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders.

BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined. METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models. RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. Immunoprofiling showed distinct baseline tumor microenvironments of MOC1 and MOC1esc1, as well as the remodeling of immune compartments on ICB in MOC1esc1 tumors. Single cell sequencing analysis identified several CD8 +TIL subsets including Tcf7 +Pd1- (naïve/memory-like), Tcf7 +Pd1+ (progenitor), and Tcf7-Pd1+ (differentiated effector). Mapping TCR shared fractions identified that successful anti-PD1 or anti-CTLA4 therapy-induced higher post-treatment T cell lineage transitions. CONCLUSIONS: These data highlight critical aspects of CD8 +TIL heterogeneity and differentiation and suggest facilitation of CD8 +TIL differentiation as a strategy to improve HNSCC ICB response.

TISMO: syngeneic mouse tumor database to model tumor immunity and immunotherapy response.

Syngeneic mouse models are tumors derived from murine cancer cells engrafted on genetically identical mouse strains. They are widely used tools for studying tumor immunity and immunotherapy response in the context of a fully functional murine immune system. Large volumes of syngeneic mouse tumor expression profiles under different immunotherapy treatments have been generated, although a lack of systematic collection and analysis makes data reuse challenging. We present Tumor Immune Syngeneic MOuse (TISMO), a database with an extensive collection of syngeneic mouse model profiles with interactive visualization features. TISMO contains 605 in vitro RNA-seq samples from 49 syngeneic cancer cell lines across 23 cancer types, of which 195 underwent cytokine treatment. TISMO also includes 1518 in vivo RNA-seq samples from 68 syngeneic mouse tumor models across 19 cancer types, of which 832 were from immune checkpoint blockade (ICB) studies. We manually annotated the sample metadata, such as cell line, mouse strain, transplantation site, treatment, and response status, and uniformly processed and quality-controlled the RNA-seq data. Besides data download, TISMO provides interactive web interfaces to investigate whether specific gene expression, pathway enrichment, or immune infiltration level is associated with differential immunotherapy response. TISMO is available at http://tismo.cistrome.org.

Integrating CD4+ T cell help for therapeutic cancer vaccination in a preclinical head and neck cancer model.

Head and neck squamous cell carcinomas (HNSCC) are well suited for cancer vaccination strategies. In addition to tumor-associated antigens (TAAs) and endogenous retrovirus (ERV) encoded proteins, HNSCCs have a relatively high tumor mutational burden encoding potential neoepitopes. Peptide vaccine candidates are prioritized by predicted high-affinity to major histocompatibility complex (MHC) class I with MHC-II affinity largely not being considered. Herein, we extend previous studies to evaluate therapeutic vaccination in the mouse oral cancer (MOC) 22 model. Two distinct MOC22 derived SLPs were tested - a TSA-oriented mutant intercellular adhesion molecule 1 (mICAM1) and p15E, an ERV encoded antigen. In silico prediction revealed mICAM1 SLP bore strong MHC-I and MHC-II epitopes sharing a mutant residue with vaccination significantly increasing both antigen-specific IFN-γ producing CD4+ and CD8+ T cells. By contrast, p15E SLP had a predicted high-affinity MHC-I epitope but lacked an MHC-II epitope and vaccination induced antigen-specific CD8+ but not CD4+ T cell responses. Therapeutic mICAM1 vaccination attenuated tumor growth effectively with mICAM1-specific T cells displaying durable IFN-γ production compared with p15E SLP. Furthermore, mICAM1 SLPs carrying weakened MHC-II binding epitopes were unable to control tumor growth. These data underscore the potential value of therapeutic targeting of HNSCC epitopes and highlight the importance of studying distinct antigen classes in this setting. Moreover, they raise the possibility that, at least in part, CD4+ T cell help is critical for cancer vaccination in this preclinical HNSCC model and suggest in silico prediction approaches prioritize overlapping MHC-I and MHC-II epitopes to generate potent cancer vaccines.

Risk Prediction in Patients With Heart Failure With Preserved Ejection Fraction Using Gene Expression Data and Machine Learning.

Heart failure with preserved ejection fraction (HFpEF) has become a major health issue because of its high mortality, high heterogeneity, and poor prognosis. Using genomic data to classify patients into different risk groups is a promising method to facilitate the identification of high-risk groups for further precision treatment. Here, we applied six machine learning models, namely kernel partial least squares with the genetic algorithm (GA-KPLS), the least absolute shrinkage and selection operator (LASSO), random forest, ridge regression, support vector machine, and the conventional logistic regression model, to predict HFpEF risk and to identify subgroups at high risk of death based on gene expression data. The model performance was evaluated using various criteria. Our analysis was focused on 149 HFpEF patients from the Framingham Heart Study cohort who were classified into good-outcome and poor-outcome groups based on their 3-year survival outcome. The results showed that the GA-KPLS model exhibited the best performance in predicting patient risk. We further identified 116 differentially expressed genes (DEGs) between the two groups, thus providing novel therapeutic targets for HFpEF. Additionally, the DEGs were enriched in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways related to HFpEF. The GA-KPLS-based HFpEF model is a powerful method for risk stratification of 3-year mortality in HFpEF patients.

Epigenetic modulation of immunotherapy and implications in head and neck cancer.

Cancer progression is facilitated by distinct mechanisms developed by cancer cells to avoid immune recognition and clearance. The clinical application of immune checkpoint blockade (ICB), via monoclonal antibodies blocking PD-1/PD-L1 and CTLA4, has achieved promising durable therapeutic response in various cancer types, including recurrent and metastatic head and neck squamous cell carcinomas (HNSCC). HNSCC represents a rational target of ICB treatment given its relatively high mutation burden and the presence of immune infiltrates. However, the limited response rates and recent negative clinical trials data identify an urgent need for new strategies to overcome immunotherapy resistance. Preclinical studies have revealed an important contribution of epigenetic regulators in the anti-tumor immune response. Multiple components of the tumor and host immune system interaction are under epigenetic regulation, including the cancer cells themselves, cytotoxic T lymphocytes, regulatory T lymphocytes, natural killer cells, and tumor-associated macrophages. Epigenetic targeting drugs such as DNA methyltransferase inhibitors, histone deacetylase, and methyltransferase inhibitors have demonstrated the potential to reverse immune suppression in various cancer models. The aim of this review is to summarize recent preclinical studies focused on investigating the function of epigenetic modulation in the host immune and cancer cell interface. We also provide a perspective on combining epigenetic modulation and immunotherapy in the management of HNSCC to improve outcomes-an area of great interest in future clinical studies.

Personalized cancer vaccination in head and neck cancer.

Cancer is characterized by an accumulation of somatic mutations that represent a source of neoantigens for targeting by antigen-specific T cells. Head and neck squamous cell carcinoma (HNSCC) has a relatively high mutation burden across all cancer types, and cellular immunity to neoantigens likely plays a key role in HNSCC clinical outcomes. Immune checkpoint inhibitors (CPIs) have brought new treatment options and hopes to patients with recurrent and/or metastatic HNSCC. However, many patients do not benefit from CPI therapies, highlighting the need for novel immunotherapy or combinatorial strategies. One such approach is personalized cancer vaccination targeting tumor-associated antigens and tumor-specific antigens, either as single agents or in combination with other therapies. Recent advances in next-generation genomic sequencing technologies and computational algorithms have enabled efficient identification of somatic mutation-derived neoantigens and are anticipated to facilitate the development of cancer vaccine strategies. Here, we review cancer vaccine approaches against HNSCC, including fundamental mechanisms of a cancer vaccine, considerations for selecting appropriate antigens, and combination therapies.

Dihydrotanshinone I inhibits ovarian cancer cell proliferation and migration by transcriptional repression of PIK3CA gene.

Dihydrotanshinone I (DHTS), extracted from Salvia miltiorrhiza, was found to be the most effective compound of tanshen extracts against cancer cells in our previous studies. However, the therapeutic benefits and underlying mechanisms of DHTS on ovarian cancer remain uncertain. In this study, we demonstrated the cytocidal effects of DHTS on chemosensitive ovarian cancer cells with or without platinum-based chemotherapy. DHTS was able to inhibit proliferation and migration of ovarian cancer cells in vitro and in vivo through modulation of the PI3K/AKT signalling pathways. Combinatorial treatment of DHTS and cisplatin exhibited enhanced DNA damage in ovarian cancer cells. Overall, these findings suggest that DHTS induces ovarian cancer cells death via induction of DNA damage and inhibits ovarian cancer cell proliferation and migration.

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.

PURPOSE: Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC. PATIENTS AND METHODS: Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10%-49%), and pTR-2 (≥50%). Coprimary endpoints were pTR-2 among all patients and 1-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (ClinicalTrials.gov NCT02296684). RESULTS: Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3-4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%-41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNγ activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients. CONCLUSIONS: Among patients with locally advanced, HPV-unrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.

Melatonin Regulates Breast Cancer Progression by the lnc010561/miR-30/FKBP3 Axis.

Melatonin has been recognized to slow breast cancer growth. The molecular mechanisms may involve long non-coding RNAs (lncRNAs). However, little is known on how melatonin affects lncRNA expression and function in breast cancer. We used microarrays to explore the expression profile of mRNAs and lncRNAs in melatonin-treated breast cancer cells. Kyoto encyclopedia of genes and genomes (KEGG) and Reactome pathways analysis were performed to identify the signaling pathways affected by altered expressed mRNAs after melatonin treatment. To explore the functions and mechanisms of the selected differentially expressed mRNA and lncRNA in breast cancer, we performed a series of experiments. We found that FK506-binding protein 3 (FKBP3) and lnc010561 were downregulated in melatonin-treated breast cancer cells. Knockdown of FKBP3 and lnc010561 inhibited breast cancer proliferation and invasion, and induced apoptosis. Also, lnc010561 and FKBP3 functioned as competing endogenous RNAs (ceRNAs) for miR-30. Our findings suggested that melatonin regulated breast cancer progression by the lnc010561/miR-30/FKBP3 axis. Melatonin may, therefore, function as an anticancer strategy for breast cancer.

Targeting EZH2 Enhances Antigen Presentation, Antitumor Immunity, and Circumvents Anti-PD-1 Resistance in Head and Neck Cancer.

PURPOSE: Anti-programmed death-1 (PD-1) receptor-based therapeutics improve survival in patients with recurrent head and neck squamous cell carcinoma (HNSCC), but many do not benefit due to a low response rate. Herein, we identified EZH2 as a therapeutic target that enhanced tumor cell antigen presentation and subsequently sensitized resistant tumors to anti-PD-1 therapy. EXPERIMENTAL DESIGN: EZH2 regulation of antigen presentation was defined using EZH2 inhibitors (GSK126 and EPZ6438) in human and mouse HNSCC cell lines. Mechanistic dissection of EZH2 in regulation of antigen presentation was investigated using flow cytometry, qRT-PCR, ELISA, and chromatin-immunoprecipitation assays. EZH2-deficient cell lines were generated using CRISPR-CAS9. GSK126 and anti-PD-1-blocking antibody were used in testing combinatorial therapy in vivo. RESULTS: EZH2 expression was negatively correlated with antigen-processing machinery pathway components in HNSCC data sets in The Cancer Genome Atlas. EZH2 inhibition resulted in significant upregulation of MHC class I expression in human and mouse human papillomavirus-negative HNSCC lines in vitro and in mouse models in vivo. Enhanced antigen presentation on the tumor cells by EZH2 inhibitors or CRISPR-mediated EZH2 deficiency increased antigen-specific CD8+ T-cell proliferation, IFNγ production, and tumor cell cytotoxicity. Mechanistically, EZH2 inhibition reduced the histone H3K27me3 modification on the ß-2-microglobulin promoter. Finally, in an anti-PD-1-resistant model of HNSCC, tumor growth was suppressed with combination therapy. CONCLUSIONS: Our results demonstrated that targeting EZH2 enhanced antigen presentation and was able to circumvent anti-PD-1 resistance. Thus, combining EZH2 targeting with anti-PD-1 may increase therapeutic susceptibility in HNSCC.

Sophorolipid biosynthesis and production from diverse hydrophilic and hydrophobic carbon substrates.

Sophorolipids (SLs), mainly synthesized by yeasts, were a sort of biosurfactant with the highest fermentation level at present. In recent years, SLs have drawn extensive attention for their excellent physiochemical properties and physiological activities. Besides, issues such as economics, sustainability, and use of renewable resources also stimulate the shift from chemical surfactants towards green or microbial-derived biosurfactants. SLs' large-scale production and application were restricted by the relatively high production costs. Currently, waste streams from agriculture, food and oil refining industries, etc., have been exploited as low-cost renewable substrates for SL production. Advanced cultivation method, uncommonly used substrates, and new genetically modified SL-producing mutants were also designed and applied to improve the productivity or the special properties of SLs. In this review, a systematic and detailed description of primary and secondary metabolism pathways involved in SL biosynthesis was summarized firstly. Furthermore, based on the pathways of SL biosynthesis from different carbon substrates, we reviewed the current knowledge and advances in the exploration of cost-effective and infrequently used hydrophilic and hydrophobic substrates for large or specialized SL production.

MiR-29 Regulates de novo Lipogenesis in the Liver and Circulating Triglyceride Levels in a Sirt1-Dependent Manner.

MicroRNAs (miRNAs) are known regulators of lipid homeostasis. We recently demonstrated that miR-29 controls the levels of circulating cholesterol and triglycerides, but the mechanisms remained unknown. In the present study, we demonstrated that systemic delivery of locked nucleic acid inhibitor of miR-29 (LNA29) through subcutaneous injection effectively suppresses hepatic expression of miR-29 and dampens de novo lipogenesis (DNL) in the liver of chow-fed mice. Next, we used mice with liver-specific deletion of Sirtuin 1 (L-Sirt1 KO), a validated target of miR-29, and demonstrated that the LNA29-induced reduction of circulating triglycerides, but not cholesterol, is dependent on hepatic Sirt1. Moreover, lipidomics analysis revealed that LNA29 suppresses hepatic triglyceride levels in a liver-Sirt1 dependent manner. A comparative transcriptomic study of liver tissue from LNA29-treated wild-type/floxed and L-Sirt1 KO mice identified the top candidate lipogenic genes and hepatokines through which LNA29 may confer its effects on triglyceride levels. The transcriptomic analysis also showed that fatty acid oxidation (FAO) genes respond differently to LNA29 depending on the presence of hepatic Sirt1. Overall, this study demonstrates the beneficial effects of LNA29 on DNL and circulating lipid levels. In addition, it provides mechanistic insight that decouples the effect of LNA29 on circulating triglycerides from that of circulating cholesterol.

Adenocarcinoma with mixed subtypes is a rare but aggressive histologic subtype in colorectal cancer.

BACKGROUND: Although numerous studies have investigated the clinicopathologic and prognostic relevance of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC) compared with classic adenocarcinoma (CA), little is known about the prognosis of adenocarcinoma with mixed subtypes (AM) and the differences among these four subtypes. METHODS: The statistics of colorectal cancer registered in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and analyzed. We also compared the clinicopathologic and prognostic relevance between CA, SRCC, MAC, and AM. RESULTS: The frequencies of these four subtypes were 69.9% (CA, n = 15,812), 25.1% (MAC, n = 5689), 3.6% (SRCC, n = 814) and 1.4% (AM, n = 321), respectively. All of MAC, SRCC, and AM were significantly related with aggressive features. Only SRCC and AM were identified as independent poor prognostic markers for overall survival by multivariate analysis. The aggressiveness of AM was between MAC and SRCC according to the clinicopathologic associations. The prognosis of AM was significantly worse than MAC but comparable with SRCC. CONCLUSIONS: We confirmed the clinicopathologic relevance with aggressive features of MAC and SRCC, as well as poor prognostic relevance of SRCC by analyzing a large study population data set. Furthermore, we identified AM as a rare but aggressive histologic subtype in colorectal cancer, to which particular attention should be given in clinical practice.

The long noncoding RNA MIR210HG promotes tumor metastasis by acting as a ceRNA of miR-1226-3p to regulate mucin-1c expression in invasive breast cancer.

BACKGROUND: Long noncoding RNAs have been known to be involved in multiple types of malignancies, including invasive breast cancer (IBC). This study aimed to explore the role of long noncoding RNAs in IBC and elucidate the potential molecular mechanisms. METHODS: Using TCGA microarray data analysis, we identified a long noncoding RNA, MIR210HG, highly expressed in IBC. Kaplan-Meier method and the log-rank test were used for survival analysis. The gain-of-function experiments were performed to assess the function of MIR210HG in IBC invasion and migration in both in vitro and in vivo settings. Bioinformatic analysis as well as luciferase reporter assay, rescue experiments and western blot assay revealed the mode of action of MIR210HG. RESULTS: The aberrantly enhanced MiR210HG expression predicted poor prognosis and lower survival rate. Knockdown of MiR210HG suppressed IBC cell invasion and metastasis both in vitro and in vivo. MiR-1226-3p was identified and validated to be the target miRNA of MiR210HG. Furthermore, MiR210HG functions as a competing endogenous RNAs (ceRNA) which sponges miR-1226-3p, therefore upregulates the expression of mucin1 (MUC1-C). CONCLUSIONS: Our study demonstrated that MiR210HG sponges miR-1226-3p to facilitate invasive breast cancer cell invasion and metastasis by regulating mucin-1c and EMT pathway, revealing the oncogenic role of MiR210HG in IBC cells.