Th1 cells contribute to retinal ganglion cell loss in glaucoma in a VCAM-1-dependent manner.

Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease.

A Bayesian model to identify multiple expression patterns with simultaneous FDR control for a multi-factor RNA-seq experiment.

It is often of research interest to identify genes that satisfy a particular expression pattern across different conditions such as tissues, genotypes, etc. One common practice is to perform differential expression analysis for each condition separately and then take the intersection of differentially expressed (DE) genes or non-DE genes under each condition to obtain genes that satisfy a particular pattern. Such a method can lead to many false positives, especially when the desired gene expression pattern involves equivalent expression under one condition. In this paper, we apply a Bayesian partition model to identify genes of all desired patterns while simultaneously controlling their false discovery rates (FDRs). Our simulation studies show that the common practice fails to control group specific FDRs for patterns involving equivalent expression while the proposed Bayesian method simultaneously controls group specific FDRs at all settings studied. In addition, the proposed method is more powerful when the FDR of the common practice is under control for identifying patterns only involving DE genes. Our simulation studies also show that it is an inherently more challenging problem to identify patterns involving equivalent expression than patterns only involving differential expression. Therefore, larger sample sizes are required to obtain the same target power to identify the former types of patterns than the latter types of patterns.

Pancancer analysis uncovers an immunological role and prognostic value of the m6A reader IGF2BP2 in pancreatic cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant gastrointestinal tumors worldwide with a dismal prognosis and high relapse rate. PDAC is considered a "cold cancer" for which immunotherapy is not effective. Therefore, to improve the prognosis for PDAC patients, it is urgent to explore the mechanism driving its insensitivity to immunotherapy. MATERIALS AND METHODS: We conducted pancancer analyses to test IGF2BP family expression and survival in patients with different cancers via TCGA and GETx databases. Then, we determined the immunological role and prognostic value of IGF2BP2 in vitro, in vivo and in clinical specimens. RESULTS: In the present study, we found that the m6A reader IGF2BP2 was the most clinically relevant member of the IGF2BP family for pancreatic cancer. High expression of IGF2BP2 was most associated with poor prognosis and an immunosuppressive microenvironment in PDAC. By IGF2BP2 knockdown, we found that tumor cell proliferation and invasive ability were significantly diminished. Importantly, we found that IGF2BP2 expression was closely associated with high expression of immunosuppressive molecules such as PD-L1. IGF2BP2 modulated downstream PD-L1 expression by regulating its mRNA stability via m6A methylation control, and we obtained the same verification in animal experiments and human tissue specimens. CONCLUSION: Our study contributes to existing knowledge regarding the IGF2BP2-regulated PD-L1 signaling pathway as a potential prognostic and immune biomarker in pancreatic cancer.

Association between serum omentin-1 and mucosal disease activity in patients with ulcerative colitis.

PURPOSE: Mucosal inflammation is a key feature of ulcerative colitis (UC), a chronic relapsing and remitting form of inflammatory bowel disease. Omentin-1, a newly discovered adipokine, is reported to have anti-inflammatory effects and has been found to be decreased in patients with inflammatory bowel disease. The aim of our study was to investigate the association between serum omentin-1 levels and mucosal disease activity in patients with UC. STUDY DESIGN: A total of 126 patients with UC and 77 healthy volunteers were enrolled in the study. Serum omentin-1 expression levels were measured using enzyme-linked immunosorbent assay to evaluate its potential for monitoring disease activity, including clinical and endoscopic activity. RESULTS: Serum omentin-1 levels were significantly lower in patients with UC compared to healthy controls (HC) (UC, 61.7 interquartile range: 51.5-72.6 versus healthy controls, 103.5 interquartile range: 48.3-156.2 ng/ml; P < .001). Furthermore, serum omentin-1 levels were associated with both clinical and endoscopic activity in patients with UC. Notably, omentin-1 levels were significantly lower in patients who achieved mucosal healing. Receiver operating characteristic curves indicated that serum omentin-1 levels could potentially serve as an activity index for evaluating UC. CONCLUSIONS: These findings provide further insight into the association between omentin-1 and UC, suggesting that omentin-1 may be a useful biomarker for monitoring mucosal disease activity in patients with UC.

Piezochromism and Conductivity Modulations under High Pressure by Manipulating the Viologen Radical Concentration.

Manipulating the radical concentration to modulate the properties in solid multifunctional materials is an attractive topic in various frontier fields. Viologens have the unique redox capability to generate radical states through reversible electron transfer (ET) under external stimuli. Herein, taking the viologens as the model, two kinds of crystalline compounds with different molecule-conjugated systems were designed and synthesized. By subjecting the specific model viologens to pressure, the cross-conjugated 2-X all exhibit much higher radical concentrations, along with more sensitive piezochromic behaviors, compared to the linear-conjugated 1-X. Unexpectedly, we find that the electrical resistance (R) of 1-NO3 decreased by three orders of magnitude with the increasing pressure, while that in high-radical-concentration 2-NO3 remained almost unchanged. To date, such unusual invariant conductivity has not been documented in molecular-based materials under high pressure, breaking the conventional wisdom that the generations of radicals are beneficial to improve conductivity. We highlight that adjusting the molecular conjugation modes can be used as an effective way to regulate the radical concentrations and thus modulate properties rationally.

Tunable Chromic Properties of Viologen-Metal Polymers Modulated by Coordination Modes for Inkless Erasable Printing.

Inkless and erasable printing (IEP) based on chromic materials holds great promise to alleviate environmental and sustainable problems. Metal-organic polymers (MOPs) are bright platforms for constructing IEP materials. However, it is still challenging to design target MOPs with excellent specific functions rationally due to the intricate component-structure-property relationships. Herein, an effective strategy was proposed for the rational design IEP-MOP materials. The stimuli-responsive viologen moiety was introduced into the construction of MOPs to give it potential chromic behaviors and two different coordination models (i. e. bilateral coordination model, M1 ; unilateral coordinated model, M2 ) based on the same viologen ligand were designed. Aided by theoretical calculations, model M1 was recommended secondarily as a more suitable system for IEP materials. Along this line, two representative viologen-ZnII MOPs 1 and 2 with models M1 and M2 were synthesized successfully. Experiments exhibit that 1 does have quicker stimuli response, stronger color contrast and longer radical lifetime compared to 2. Significantly, the obtained 1-IEP media brightly inherits the excellent chromic characteristics of 1 and the flexibility of the paper at the same time, which achieves most daily printing requirements, as well as enough resolution and durability to be used in identification by smart device.

Glutamate from nerve cells promotes perineural invasion in pancreatic cancer by regulating tumor glycolysis through HK2 mRNA-m6A modification.

BACKGROUND: Perineural invasion (PNI) has a high incidence and poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Our study aimed to identify the underlying molecular mechanism of PNI and propose effective intervention strategies. METHODS: To observe PNI in vitro and in vivo, a Matrigel/ dorsal root ganglia (DRG) model and a murine sciatic nerve invasion model were respectively used. Magnetic resonance (MR) imaging and positron emission tomography/computed tomography (PET-CT) imaging were also used to evaluate tumor growth. Publicly available datasets and PDAC tissues were used to verify how the nerve cells regulate PDAC cells' PNI. RESULTS: Our results showed that glutamate from nerve cells could cause calcium influx in PDAC cells via the N-methyl-d-aspartate receptor (NMDAR), subsequently activating the downstream Ca2+ dependent protein kinase CaMKII/ERK-MAPK pathway and promoting the mRNA transcription of gene METTL3. Next, METTL3 upregulates the expression of hexokinase 2 (HK2) through N6-methyladenosine (m6A) modification in mRNA, enhances the PDAC cells' glycolysis, and promotes PNI. Furthermore, the IONPs-PEG-scFvCD44v6-scAbNMDAR2B nanoparticles dual targeting CD44 variant isoform 6 (CD44v6) and t NMDAR subunit 2B (NMDAR2B) on PDAC cells were synthesized and verified showing a satisfactory blocking effect on PNI. CONCLUSIONS: Here, we firstly provided evidence that glutamate from the nerve cells could upregulate the expression of HK2 through mRNA m6A modification via NMDAR2B and downstream Ca2+ dependent CaMKII/ERK-MAPK pathway, enhance the glycolysis in PDAC cells, and ultimately promote PNI. In addition, the dual targeting nanoparticles we synthesized were verified to block PNI effectively in PDAC.

Simultaneous removal of nitrate, lead, and tetracycline by a fixed-biofilm reactor assembled with kapok fiber and sponge iron: Comparative analysis of operating conditions and biotic community.

In recent years, under the condition of lack of carbon source, the presence of composite micro-pollutants make the removal of nitrate seriously damaged, and to find a suitable way to solve this problem is imminent. A fixed-biofilm carrier modified by mixing sponge iron (SI) and kapok fiber (KF) combined with strain Zoogloea sp. FY6 was constructed in this study to get a fixed-biofilm reactor with merit denitrification performance. By adjusting the operation parameters, it can be concluded that when the carbon to nitrogen (C/N) ratio was 1.5, the hydraulic retention time (HRT) was 6.0 h, and the pH was 6.0, the nitrate removal efficiency (NRE) of the fixed-biofilm reactor was up to 95.4% (2.95 mg L-1 h-1). In addition, the fixed-biofilm reactor constructed in this study can remove lead (Pb2+) and tetracycline (TC) excellently in the presence of SI and Zoogloea sp. FY6, and the denitrification performance can still maintain a high level under the influence of different concentrations of Pb2+ and TC. Furthermore, the addition of SI not only removes the compound pollutants, but also protects the toxicity of the pollutant inflow in the bioreactor, and the metabolic process of microorganisms in the bioreactor also removes some of the compound pollutants. The high-throughput data showed the abundance of strain Zoogloea sp. FY6 was still the highest value under the influence of various pollutants, and the metagenomic prediction showed that the fixed-biofilm reactor had perfect denitrification process and iron redox cycle benefits. This study provides a valuable reference for sustainable utilization of natural biological resources and reduction of material costs in wastewater treatment plants (WWTPs).

H3K36 methylation promotes longevity by enhancing transcriptional fidelity.

Epigenetic mechanisms, including histone post-translational modifications, control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an emerging phenomenon of shortened life span, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a life span screen in Saccharomyces cerevisiae that is designed to identify amino acid residues of histones that regulate yeast replicative aging. Our results reveal that lack of sustained histone H3K36 methylation is commensurate with increased cryptic transcription in a subset of genes in old cells and with shorter life span. In contrast, deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes, suppresses cryptic transcript initiation, and extends life span. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to loss of transcriptional precision that is detrimental to life span, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity.

Regulation pore size distribution for facilitating malachite green removal on carbon foam.

Malachite green (MG) is widely used as a textile dye and an aquacultural biocide, and become a serious pollution of drink water, but effectually isolating and removing it from wastewater are still a challenge. Here we report a new strategy to prepare a carbon foam with tunable pore size distribution by a one-pot lava foam process. We find that uniform micropore size is beneficial to the formation of C-OH coordination on the pore surface, increasing MG adsorption rates via H+ ionization. As a result, carbon foam with uniform pore size distribution demonstrates an optimum MG removal efficiency of 1812 mg g-1 and a higher partition coefficient of 3.02 mg g-1 µM-1, which is twice that of carbon foams with irregular pore size distribution. The adsorption of MG onto these adsorbents was found to be an endothermic monolayer chemical adsorption process, and the Gibbs free energy of adsorption process was decreased obviously by regulating micropore size distribution. The experiment results are in good agreement with pseudo-second-order kinetic and Langmuir isotherm models. Revealed the pore size distribution was the critical factor of MG removal by carbon foam. It should be and inspiration for the design and development of highly efficiency adsorbents for dyes removal.

Asymmetric Distribution of Gene Trees Can Arise under Purifying Selection If Differences in Population Size Exist.

Incomplete lineage sorting (ILS) is an important factor that causes gene tree discordance. For gene trees of three species, under neutrality, random mating, and the absence of interspecific gene flow, ILS creates a symmetric distribution of gene trees: the gene tree that accords with the species tree has the highest frequency, and the two discordant trees are equally frequent. If the neutral condition is violated, the impact of ILS may change, altering the gene tree distribution. Here, we show that under purifying selection, even assuming that the fitness effect of mutations is constant throughout the species tree, if differences in population size exist among species, asymmetric distributions of gene trees will arise, which is different from the expectation under neutrality. In extremes, one of the discordant trees rather than the concordant tree becomes the most frequent gene tree. In addition, we found that in a real case, the position of Scandentia relative to Primate and Glires, the symmetry in the gene tree distribution can be influenced by the strength of purifying selection. In current phylogenetic inference, the impact of purifying selection on the gene tree distribution is rarely considered by researchers. This study highlights the necessity of considering this impact.

Translational control of lipogenic enzymes in the cell cycle of synchronous, growing yeast cells.

Translational control during cell division determines when cells start a new cell cycle, how fast they complete it, the number of successive divisions, and how cells coordinate proliferation with available nutrients. The translational efficiencies of mRNAs in cells progressing synchronously through the mitotic cell cycle, while preserving the coupling of cell division with cell growth, remain uninvestigated. We now report comprehensive ribosome profiling of a yeast cell size series from the time of cell birth, to identify mRNAs under periodic translational control. The data reveal coordinate translational activation of mRNAs encoding lipogenic enzymes late in the cell cycle including Acc1p, the rate-limiting enzyme acetyl-CoA carboxylase. An upstream open reading frame (uORF) confers the translational control of ACC1 and adjusts Acc1p protein levels in different nutrients. The ACC1 uORF is relevant for cell division because its ablation delays cell cycle progression, reduces cell size, and suppresses the replicative longevity of cells lacking the Sch9p protein kinase regulator of ribosome biogenesis. These findings establish an unexpected relationship between lipogenesis and protein synthesis in mitotic cell divisions.

RORγt Represses IL-10 Production in Th17 Cells To Maintain Their Pathogenicity in Inducing Intestinal Inflammation.

The role of retinoid-related orphan receptor γ t (RORγt) in Th17 cell differentiation has been well established; however, how it regulates other T cell lineages is still not clearly understood. In this study, we report that in mice, while promoting Th17 cell differentiation, RORγt inhibited IL-10 production by T cells, thereby preserving the pathogenicity of Th17 cells. Treatment with RORγt-specific inhibitor suppressed Th17 cell signature cytokines, but promoted IL-10 production. RORγt inhibitor-treated Th17 cells induce less severe colitis compared with control Th17 cells. Mechanistically, the RORγt inhibitor induced T cell expression of Blimp-1 (encoded by Prdm1). Prdm1-/- T cells produced significantly fewer IL-10 when treated with RORγt inhibitor compared with wild-type T cells. Furthermore, RORγt inhibitor-treated Prdm1-/- Th17 cells induce more severe colitis compared with RORγt inhibitor-treated wild-type Th17 cells. Collectively, our studies reveal a novel mechanism by which RORγt drives and maintains pathogenic Th17 cell development by inhibiting IL-10 production.

Characteristics of inorganic matter from Australian municipal solid waste processed under combustion and gasification conditions.

The presence and composition of ash in solid waste streams produced by the thermochemical processes can affect the further disposal or use of the waste. This study characterised the chemical species, mineralogy and trace element mobilisation in laboratory-produced ashes arising from different municipal solid waste (MSW) streams processed under reducing and oxidising atmospheres.The composition of cumulative ash samples produced under oxidising conditions was very similar to the composition of the industrial bottom ash samples produced during MSW incineration. We identified differences in mineral phase compositions and in some trace element concentrations of ashes produced under combustion and gasification conditions. Differences in concentrations of boron, barium, cadmium, chromium, copper, chlorine, molybdenum, antimony, lead, thorium and zinc in ashes associated with different MSW streams were also observed. On the basis of the concentrations of trace elements in ashes, we evaluated each MSW stream in terms of potential management strategies and use of the mineral matter remaining after combustion and gasification. Most of ashes produced from MSW can be at least classified as Class IV (secure) waste according to an Australian standard regulation guideline.

PairedFB: a full hierarchical Bayesian model for paired RNA-seq data with heterogeneous treatment effects.

MOTIVATION: Several methods have been proposed for the paired RNA-seq analysis. However, many of them do not consider the heterogeneity in treatment effect among pairs that can naturally arise in real data. In addition, it has been reported in literature that the false discovery rate (FDR) control of some popular methods has been problematic. In this paper, we present a full hierarchical Bayesian model for the paired RNA-seq count data that accounts for variation of treatment effects among pairs and controls the FDR through the posterior expected FDR. RESULTS: Our simulation studies show that most competing methods can have highly inflated FDR for small to moderate sample sizes while PairedFB is able to control FDR close to the nominal levels. Furthermore, PairedFB has overall better performance in ranking true differentially expressed genes (DEGs) on the top than others, especially when the sample size gets bigger or when the heterogeneity level of treatment effects is high. In addition, PairedFB can be applied to identify the biologically significant DEGs with controlled FDR. The real data analysis also indicates PairedFB tends to find more biologically relevant genes even when the sample size is small. PairedFB is also shown to be robust with respect to the model misspecification in terms of its relative performance compared to others. AVAILABILITY AND IMPLEMENTATION: Software to implement this method (PairedFB) can be downloaded at: https://sites.google.com/a/udel.edu/qiujing/publication. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Bi-layer metasurface based on Huygens' principle for high gain antenna applications.

A planar isotropic unit cell based on Huygens' principle is presented for achieving transmission phase control. By tailoring overlapping electric and magnetic resonances with geometry of the proposed unit cell, the transmission phase ranging from 0 - 2π is achieved with high transmittance. The proposed unit cell is then employed to design a metasurface lens with center frequency at 9.3 GHz and a square shaped patch antenna is placed at the focal point of the designed lens to perform conversion from spherical wave front of the source antenna to planar wave front. The designed lens antenna is capable to realize pencil beam radiation pattern with a gain of 19.6 dB and side lobe levels less than -15 dB in simulation. To experimentally verify the proposed design, a prototype of the metasurface lens is fabricated and measured. The measurement results well validate the proposed design and its enhanced performance.

Double-arrow metasurface for dual-band and dual-mode polarization conversion.

We present experimentally a double-arrow metasurface for high-efficiently manipulating the polarization states of electromagnetic waves in the dual-band. The metasurface is capable of converting a linearly polarized (LP) incident wave into a circularly polarized (CP) wave or its cross-polarized LP wave at different frequencies. It is numerically shown that in the two bands from 14.08 to 15.71 GHz and from 17.63 to 19.55 GHz the metasurface can convert the LP wave into CP wave, of which the axis ratio is lower than 3 dB. Meanwhile, the proposed metasurface also can convert the LP wave into its cross-polarized LP wave at 13.39 GHz and 20.29 GHz. To validate the theoretical analysis and simulated results, a prototype is fabricated and measured. The experimental results are reasonably consistent with the theoretical and simulated results, which demonstrates that such a metasurface can successfully achieve dual-band and dual-mode polarization conversion.

MicroRNA-125a suppresses intestinal mucosal inflammation through targeting ETS-1 in patients with inflammatory bowel diseases.

MicroRNA (miR)-125a is highly expressed in T cells and regulates the functions of Treg through the IL-6-STAT3 signaling pathway. However, the role of miR-125a in regulating immune responses in intestinal mucosa of patients with inflammatory bowel diseases (IBD) is still not understood. Here we showed that miR-125a expression was decreased in PBMC and inflamed intestinal mucosa from IBD patients compared with that in healthy controls. Transduction with LV-miR-125a into IBD CD4+ T cells could significantly inhibit proinflammatory cytokine production, including IFN-γ, TNF-α and IL-17A. RNA-seq analysis of miR-125a-/- CD4+ T cells revealed enhanced genes (e.g., Stat1, Stat3, RORγt, Irf4, Klf13) in T cell activation and effector pathways, while ETS-1 as its functional target promoted IBD CD4+ T cell differentiation into Th1 cells. Consistently, miR-125a-/- mice developed more severe colitis induced by TNBS compared with WT mice. Thus, our data suggest that miR-125a protects intestinal mucosa from inflammatory injury and that ETS-1 as its target participates in the pathogenesis of IBD.

Recoverable impacts of ocean acidification on the tubeworm, Hydroides elegans: implication for biofouling in future coastal oceans.

Ocean uptake of anthropogenic CO2 causes ocean acidification (OA), which not only decreases the calcification rate, but also impairs the formation of calcareous shells or tubes in marine invertebrates such as the dominant biofouling tubeworm species, Hydroides elegans. This study examined the ability of tubeworms to resume normal tube calcification when returned to ambient pH 8.1 from a projected near-future OA level of pH 7.8. Tubeworms produced structurally impaired and mechanically weaker calcareous tubes at pH 7.8 compared to at pH 8.1, but were able to recover when the pH was restored to ambient levels. This suggests that tubeworms can physiologically recover from the impacts of OA on tube calcification, composition, density, hardness and stiffness when returned to optimal conditions. These results help understanding of the progression of biofouling communities dominated by tubeworms in future oceans with low pH induced by OA.

MicroRNA 301A Promotes Intestinal Inflammation and Colitis-Associated Cancer Development by Inhibiting BTG1.

BACKGROUND & AIMS: Intestinal tissues from patients with inflammatory bowel disease (IBD) and colorectal cancer have increased expression of microRNA-301a (MIR301A) compared with tissues from patients without IBD. We studied the mechanisms of MIR301A in the progression of IBD in human tissues and mice. METHODS: We isolated intestinal epithelial cells (IECs) from biopsy samples of the colon from 153 patients with different stages of IBD activity, 6 patients with colitis-associated cancer (CAC), and 35 healthy individuals (controls), enrolled in the study in Shanghai, China. We measured expression of MIR301A and BTG anti-proliferation factor 1 (BTG1) by IECs using quantitative reverse-transcription polymerase chain reaction. Human colon cancer cell lines (HCT-116 and SW480) were transfected with a lentivirus that expresses MIR301A; expression of cytokines and tight junction proteins were measured by quantitative reverse transcription polymerase chain reaction, flow cytometry, and immunofluorescence staining. We generated mice with disruption of the microRNA-301A gene (MIR301A-knockout mice), and also studied mice that express a transgene-encoding BTG1. Colitis was induced in knockout, transgenic, and control (C57BL/B6) mice by administration of dextran sulfate sodium (DSS), and mice were given azoxymethane to induce colorectal carcinogenesis. Colons were collected and analyzed histologically and by immunohistochemistry; tumor nodules were counted and tumor size was measured. SW480 cells expressing the MIR301A transgene were grown as xenograft tumors in nude mice. RESULTS: Expression of MIR301A increased in IECs from patients with IBD and CAC compared with controls. MIR301A-knockout mice were resistant to the development of colitis following administration of DSS; their colon tissues expressed lower levels of interleukin 1ß (IL1ß), IL6, IL8, and tumor necrosis factor than colons of control mice. Colon tissues from MIR301A-knockout mice had increased epithelial barrier integrity and formed fewer tumors following administration of azoxymethane than control mice. Human IECs expressing transgenic MIR301A down-regulated expression of cadherin 1 (also called E-cadherin or CDH1). We identified BTG1 mRNA as a target of MIR301A; levels of BTG1 mRNA were reduced in inflamed mucosa from patients with active IBD compared with controls. There was an inverse correlation between levels of BTG1 mRNA and levels of MIR301A in inflamed mucosal tissues from patients with active IBD. Human colon cancer cell lines that expressed a MIR301A transgene increased proliferation; they had increased permeability and decreased expression of CDH1 compared with cells transfected with a control vector, indicating reduced intestinal barrier function. BTG1 transgenic mice developed less severe colitis than control mice following administration of DSS. SW480 cells expressing anti-MIR301A formed fewer xenograft tumors in nude mice than cells expressing a control vector. CONCLUSIONS: Levels of MIR301A are increased in IECs from patients with active IBD. MIR301A reduces expression of BTG1 to reduce epithelial integrity and promote inflammation in mouse colon and promotes tumorigenesis. Strategies to decrease levels of MIR301A in colon tissues might be developed to treat patients with IBD and CAC.