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The biological role of miR-500a-5p has not yet been reported in the context of colorectal cancer (CRC). Here, we show that miR-500a-5p expression is decreased in CRC tissues compared with adjacent normal tissues. Low miR-500a-5p expression is associated with malignant progression. Moreover, transfection of CRC cells with miR-500a-5p induces G0/G1 cell cycle arrest and inhibits their growth and migration. Mechanistically, miR-500a-5p directly targets HDAC2 and inhibits HDAC2-mediated proliferation in CRC in nude mice. Furthermore, YY1 binds to the promoter of miR-500a-5p and negatively regulates its transcription. Restoration of miR-500a-5p expression is up-regulated via the p300/YY1/HDAC2 complex. Besides, therapeutic delivery of miR-500a-5p significantly suppresses tumour development in a xenograft tumour model and a HDAC2 inhibitor FK228-treated CRC model. Our studies demonstrate that miR-500a-5p functions as a tumour suppressor in CRC by targeting the p300/YY1/HDAC2 axis, which contributes to the development of and provides new potential candidates for CRC therapy. MicroRNA miR-500a-5p has been linked to oncogenesis but its role in colorectal cancer (CRC) is largely unknown. Here, the authors investigate the role of miR-500a-5p in CRC in vitro and in vivo models and find that miR-500a-5p acts as a tumour suppressor in CRC by targeting the p300/YY1/HDAC2 axis.

Background and aims Improving the rate of polyp detection is an important measure to prevent colorectal cancer (CRC). Real-time automatic polyp detection systems, through deep learning methods, can learn and perform specific endoscopic tasks previously performed by endoscopists. The purpose of this study was to explore whether a high-performance, real-time automatic polyp detection system could improve the polyp detection rate (PDR) in the actual clinical environment. Methods The selected patients underwent same-day, back-to-back colonoscopies in a random order, with either traditional colonoscopy or artificial intelligence (AI)-assisted colonoscopy performed first by different experienced endoscopists (> 3000 colonoscopies). The primary outcome was the PDR. It was registered with clinicaltrials.gov . (NCT047126265). Results In this study, we randomized 150 patients. The AI system significantly increased the PDR (34.0% vs 38.7%, p < 0.001). In addition, AI-assisted colonoscopy increased the detection of polyps smaller than 6 mm (69 vs 91, p < 0.001), but no difference was found with regard to larger lesions. Conclusions A real-time automatic polyp detection system can increase the PDR, primarily for diminutive polyps. However, a larger sample size is still needed in the follow-up study to further verify this conclusion. Trial Registration clinicaltrials.gov Identifier: NCT047126265

Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of SMS in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis and causes tumor regression, but these effects are profoundly attenuated by silencing Bim . These findings uncover a key survival signal in CRC through convergent repression of Bim expression by distinct SMS- and MYC-mediated signaling pathways. Thus, combined inhibition of SMS and MYC signaling may be an effective therapy for CRC. Polyamine metabolism is frequently dysregulated in cancers. Here, the authors show that a polyamine biosynthetic enzyme, spermine synthase, is overexpressed in colorectal cancers and cooperates with MYC to prevent cancer cell apoptosis by repression of proapoptotic protein, Bim.

DDX39B is a member of the DEAD box (DDX) RNA helicase family required for nearly all cellular RNA metabolic processes. The exact role and potential molecular mechanism of DDX39B in the progression of human colorectal cancer (CRC) remain to be investigated. In the present study, we demonstrate that DDX39B expression is higher in CRC tissues than in adjacent normal tissues. Gain- and loss-of-function assays revealed that DDX39B facilitates CRC metastasis in vivo and in vitro. Mechanistically, RNA-sequencing (RNA-seq) and RNA-binding protein immunoprecipitation-sequencing (RIP-seq) showed that DDX39B binds directly to the FUT3 pre-mRNA and upregulates FUT3 expression. Splicing experiments in vitro using a Minigene assay confirmed that DDX39B promotes FUT3 pre-mRNA splicing. A nuclear and cytoplasmic RNA separation assay indicates that DDX39B enhances the mRNA export of FUT3. Upregulation of FUT3 accelerates the fucosylation of TGFβR-I, which activates the TGFβ signaling pathway and eventually drives the epithelial–mesenchymal transition (EMT) program and contributes to CRC progression. These findings not only provide new insight into the role of DDX39B in mRNA splicing and export as well as in tumorigenesis, but also shed light on the effects of aberrant fucosylation on CRC progression.

The Glucose-to-Albumin Ratio (GAR) has been identified as a significant predictor among sepsis and nonalcoholic fatty liver disease. However, its utility in predicting all-cause mortality among patients with acute pancreatitis (AP) has not been studied. Consequently, this study aimed to evaluate the predictive value of GAR for 28-day mortality among AP patients. This retrospective cohort study used data from the Medical Information Mart for Intensive Care (MIMIC-IV) database. According to the median GAR value, participants were divided into two cohorts. The primary endpoint was all-cause mortality within 28 days. Kaplan–Meier survival analysis and the log-rank test were employed to compare survival between the two cohorts. Cox proportional hazards models were then applied to estimate the hazard ratio of GAR, with and without adjustment for other significant clinical factors. Subgroup analyses were conducted to evaluate the relationship between GAR and mortality within strata of other significant factors. Finally, receiver operating characteristic (ROC) curves based on a logistic regression model were constructed to assess the predictive capability of GAR using the area under the curve (AUC), which was then compared with other predictors. A total of 459 patients with AP were included in the study. Kaplan–Meier curves and the log-rank test demonstrated that patients with a high GAR (> 48.85) had significantly higher 28-day all-cause mortality than those with a low GAR ( p  = 0.026). Cox proportional hazards models further indicated that high binary GAR was associated with an increased unadjusted hazard ratio (HR = 2.006, p  = 0.029). When treated as a continuous variable, higher GAR remained significantly associated with an elevated hazard ratio after adjusting for age, gender, race, and BMI (HR = 1.010, p  = 0.007). This association persisted in the final adjusted model derived through backward selection, where higher GAR continued to predict higher 28-day mortality risk (HR = 1.010, p  = 0.008) after controlling for age, gender, race, BMI, and prothrombin time (PT). Subgroup analyses revealed no significant interaction between binary GAR and other covariates in predicting 28-day mortality. Compared with glucose, albumin, the Systemic Inflammatory Response Syndrome score, and the Glasgow Coma Scale score, GAR demonstrated superior predictive power, with a higher AUC (0.602) for predicting 28-day mortality. Our study originally identified that elevated GAR was correlated with increased 28-day all-cause mortality among AP patients, and GAR demonstrated strong predictive value for short-term mortality risk.

In the present report, we show that the human fecal microbiota contains promising and universal biomarkers for the noninvasive evaluation of inflammatory bowel disease severity and IFX treatment efficacy, emphasizing the potential ability to mine the gut microbiota as a modality to stratify IBD patients and apply personalized therapy for optimal outcomes. Gut microbiota dysbiosis contributes to the onset and perpetuation of inflammatory bowel disease (IBD). Given that gut microbiotas vary across geography and ethnicity, it remains obscure whether any universal microbial signatures for IBD diagnosis and prognosis evaluation exist irrespective of populations. Here we profiled the fecal microbiota of a series of Chinese IBD patients and combined them with two Western IBD cohorts, PRISM and RISK, for meta-analyses. We found that the gut microbial alteration patterns in IBD are similar among Chinese and Westerners. Our prediction model based on gut microbiome for IBD diagnosis is robust across the cohorts, which showed 87.5% and 79.1% prediction accuracy in Crohn’s disease (CD) and ulcerative colitis (UC) patients, respectively. A relative increase in the levels of Actinobacteria and Proteobacteria ( Enterobacteriaceae ) and a relative decrease in the levels of Firmicutes ( Clostridiales ) were strongly correlated with IBD severity ( P < 0.05). Additionally, restoration of gut microbiota diversity and a significant increase in Clostridiales relative abundance were found in patients responding to infliximab (IFX [Remicade]) treatment compared to those in relapse. Moreover, certain microbes, mainly Clostridiales , predicted the treatment effectiveness with 86.5% accuracy alone and 93.8% accuracy in combination with calprotectin levels and Crohn’s disease activity index (CDAI). Taking the results together, we conclude that gut microbiota can offer a set of universal biomarkers for diagnosis, disease activity evaluation, and infliximab treatment response prediction in IBD. IMPORTANCE In the present report, we show that the human fecal microbiota contains promising and universal biomarkers for the noninvasive evaluation of inflammatory bowel disease severity and IFX treatment efficacy, emphasizing the potential ability to mine the gut microbiota as a modality to stratify IBD patients and apply personalized therapy for optimal outcomes.

The current tumour-node-metastasis (TNM) staging system alone cannot provide adequate information for prognosis and adjuvant chemotherapy benefits in patients with gastric cancer (GC). Pathomics, which is based on the development of digital pathology, is an emerging field that might improve clinical management. Herein, we propose a pathomics signature (PS GC ) that is derived from multiple pathomics features of haematoxylin and eosin-stained slides. We find that the PS GC is an independent predictor of prognosis. A nomogram incorporating the PS GC and TNM staging system shows significantly improved accuracy in predicting the prognosis compared to the TNM staging system alone. Moreover, in stage II and III GC patients with a low PS GC (but not in those with a high PS GC ), satisfactory chemotherapy benefits are observed. Therefore, the PS GC could serve as a prognostic predictor in patients with GC and might be a potential predictive indicator for decision-making regarding adjuvant chemotherapy. The current tumour-node-metastasis staging system alone cannot provide adequate information for prognosis and adjuvant chemotherapy benefits in patients with gastric cancer. Herein, the authors propose a pathomics signature that was derived from multiple features of haematoxylin and eosin-stained slides.

It is well recognized that hypoxia-inducible factor 1 alpha (HIF-1α) is involved in cancer metastasis, chemotherapy and poor prognosis. We previously found that deferoxamine, a hypoxia-mimetic agent, induces epithelial-mesenchymal transition (EMT) in colorectal cancer. Therefore, here we explored a new molecular mechanism for HIF-1α contributing to EMT and cancer metastasis through binding to ZEB1. In this study, we showed that overexpression of HIF-1α with adenovirus infection promoted EMT, cell invasion and migration in vitro and in vivo. On a molecular level, HIF-1α directly binding to the proximal promoter of ZEB1 via hypoxia response element (HRE) sites thus increasing the transactivity and expression of ZEB1. In addition, inhibition of ZEB1 was able to abrogate the HIF-1α-induced EMT and cell invasion. HIF-1α expression was highly correlated with the expression of ZEB1 in normal colorectal epithelium, primary and metastatic CRC tissues. Interestingly, both HIF-1α and ZEB1 were positively associated with Vimentin, an important mesenchymal marker of EMT, whereas negatively associated with E-cadherin expression. These findings suggest that HIF-1α enhances EMT and cancer metastasis by binding to ZEB1 promoter in CRC. HIF-1α and ZEB1 are both widely considered as tumor-initiating factors, but our results demonstrate that ZEB1 is a direct downstream of HIF-1α, suggesting a novel molecular mechanism for HIF-1α-inducing EMT and cancer metastasis.

BackgroundWireless capsule endoscopy (WCE) is considered to be a powerful instrument for the diagnosis of intestine diseases. Convolution neural network (CNN) is a type of artificial intelligence that has the potential to assist the detection of WCE images. We aimed to perform a systematic review of the current research progress to the CNN application in WCE.MethodsA search in PubMed, SinoMed, and Web of Science was conducted to collect all original publications about CNN implementation in WCE. Assessment of the risk of bias was performed by Quality Assessment of Diagnostic Accuracy Studies-2 risk list. Pooled sensitivity and specificity were calculated by an exact binominal rendition of the bivariate mixed-effects regression model. I2 was used for the evaluation of heterogeneity.Results16 articles with 23 independent studies were included. CNN application to WCE was divided into detection on erosion/ulcer, gastrointestinal bleeding (GI bleeding), and polyps/cancer. The pooled sensitivity of CNN for erosion/ulcer is 0.96 [95% CI 0.91, 0.98], for GI bleeding is 0.97 (95% CI 0.93–0.99), and for polyps/cancer is 0.97 (95% CI 0.82–0.99). The corresponding specificity of CNN for erosion/ulcer is 0.97 (95% CI 0.93–0.99), for GI bleeding is 1.00 (95% CI 0.99–1.00), and for polyps/cancer is 0.98 (95% CI 0.92–0.99).ConclusionBased on our meta-analysis, CNN-dependent diagnosis of erosion/ulcer, GI bleeding, and polyps/cancer approached a high-level performance because of its high sensitivity and specificity. Therefore, future perspective, CNN has the potential to become an important assistant for the diagnosis of WCE.

Background Crosstalk between cancer cells and tumor-associated macrophages (TAMs) mediates tumor progression in colorectal cancer (CRC). Cytoplasmic polyadenylation element binding protein 3 (CPEB3) has been shown to exhibit tumor-suppressive role in CRC. Methods The expression of CPEB3, CD68, CD86 and CD163 was determined in CRC tissues. SW480 or HCT116 cells overexpressing CPEB3 and LoVo or RKO cells with CPEB3 knockdown were constructed. Stably transfected CRC cells were co-cultured with THP-1 macrophages to determine the malignant phenotype of CRC cells, macrophage polarization, and secretory signals. The inhibition of CPEB3 on tumor progression and M2-like TAM polarization was confirmed in nude mice. Results Decreased CPEB3 expression in CRC was associated with fewer CD86 + TAMs and more CD163 + TAMs. CPEB3 knockdown in CRC cells increased the number of CD163 + TAMs and the expression of IL1RA, IL-6, IL-4 and IL-10 in TAM supernatants. TAMs enhanced CRC cell proliferation and invasion via IL-6, and then activated the IL-6R/STAT3 pathway in CRC cells. However, CPEB3 reduced the IL-6R protein levels by directly binding to IL-6R mRNA, leading to decreased phosphorylated-STAT3 expression in CRC cells. CCL2 was significantly increased in CPEB3 knockdown cells, while CCL2 antibody treatment rescued the effect of CPEB3 knockdown in promoting CD163 + TAM polarization. Eventually, we confirmed that CPEB3 inhibits tumor progression and M2-like TAM polarization in vivo. Conclusions CPEB3 is involved in the crosstalk between CRC cells and TAMs by targeting IL-6R/STAT3 signaling.