JAML inhibits colorectal carcinogenesis by modulating the tumor immune microenvironment.

It is necessary to explore new targets for the treatment of colon adenocarcinoma (COAD) according to the tumor microenvironment. The expression levels of JAML and CXADR were analyzed by bioinformatics analysis and validation of clinical samples. JAML over-expression CD8+ T cell line was constructed, and the proliferation activity was detected by MTT. The production of inflammatory factors was detected by ELISA. The expression of immune checkpoint PD-1 and TIM-3 was detected by Western blot. The apoptosis level was detected by flow cytometry and apoptosis markers. The AOM/DSS mouse model of colorectal cancer was constructed. The expression levels of JAML, CXADR and PD-1 were detected by PCR and Western blot, and the proportion of CD8+ T cells and exhausted T cells were detected by flow cytometry. The expression levels of JAML and CXADR were significantly decreased in colon cancer tissues. Overexpression of JAML can promote the proliferation of T cells, secrete a variety of inflammatory factors. Overexpression of CXADR can reduce the proliferation of colorectal cancer cells, promote apoptosis, and down-regulate the migration and invasion ability of tumor cells. Both JAML agonists and PD-L1 inhibitors can effectively treat colorectal cancer, and the combined use of JAML agonists and PD-L1 inhibitors can enhance the effect. JAML can promote the proliferation and toxicity of CD8+ T cells and down-regulate the expression of immune checkpoints in colon cancer. CXADR can inhibit the proliferation of cancer cells and promote the apoptosis. JAML agonist can effectively treat colorectal cancer by regulating CD8+ T cells.

Dysregulation and antimetastatic function of circLRIG1 modulated by miR-214-3p/LRIG1 axis in bladder carcinoma.

CircLRIG1, a newly discovered circRNA, has yet to have its potential function and biological processes reported. This study explored the role of circLRIG1 in the development and progression of bladder carcinoma and its potential molecular mechanisms. Techniques such as qRT-PCR, Western blot, various cellular assays, and in vivo models were used to investigate mRNA and protein levels, cell behavior, molecular interactions, and tumor growth. The results showed that both circLRIG1 and LRIG1 were significantly reduced in bladder carcinoma tissues and cell lines. Low circLRIG1 expression was associated with poor patient prognosis. Overexpressing circLRIG1 inhibited bladder carcinoma cell growth, migration, and invasion, promoted apoptosis, and decreased tumor growth and metastasis in vivo. Importantly, circLRIG1 was found to sponge miR-214-3p, enhancing LRIG1 expression, and its overexpression also modulated protein levels of E-cadherin, N-cadherin, Vimentin, and LRIG1. Similar effects were observed with LRIG1 overexpression. Notably, a positive correlation was found between circLRIG1 and LRIG1 expression in bladder carcinoma tissues. Additionally, the tumor-suppressing effect of circLRIG1 was reversed by overexpressing miR-214-3p or silencing LRIG1. The study concludes that circLRIG1 suppresses bladder carcinoma progression by enhancing LRIG1 expression via sponging miR-214-3p, providing a potential strategy for early diagnosis and treatment of bladder carcinoma.

ING3 inhibits the malignant progression of lung adenocarcinoma by negatively regulating ITGB4 expression to inactivate Src/FAK signaling.

Lung adenocarcinoma (LUAD) is the most commonly diagnosed subtype of lung cancer worldwide. Inhibitor of growth 3 (ING3) serves as a tumor suppressor in many cancers. This study aimed to elucidate the role of ING3 in the progression of LUAD and investigate the underlying mechanism related to integrin ß4 (ITGB4) and Src/focal adhesion kinase (FAK) signaling. ING3 expression in LUAD tissues and the correlation between ING3 expression and prognosis were analyzed by bioinformatics databases. After evaluating ING3 expression in LUAD cells, ING3 was overexpressed to assess the proliferation, cell cycle arrest, migration and invasion of LUAD cells. Then, ITGB4 was upregulated to observe the changes of malignant activities in ING3-overexpressed LUAD cells. The transplantation tumor model of NCI-H1975 cells in nude mice was established to analyze the antineoplastic effect of ING3 upregulation in vivo. Downregulated ING3 expression was observed in LUAD tissues and cells and lower ING3 expression predicated the poor prognosis. ING3 upregulation restrained the proliferation, migration, invasion and induced the cell cycle arrest of NCI-H1975 cells. Additionally, ITGB4 expression was negatively correlated with ING3 expression in LUAD tissue. ING3 led to reduced expression of ITGB4, Src and p-FAK. Moreover, ITGB4 overexpression alleviated the effects of ING3 upregulation on the malignant biological properties of LUAD cells. It could be also found that ING3 upregulation limited the tumor volume, decreased the expression of ITGB4, Src and p-FAK, which was restored by ITGB4 overexpression. Collectively, ING3 inhibited the malignant progression of LUAD by negatively regulating ITGB4 expression to inactivate Src/FAK signaling.

Risk of Mycoplasma pneumoniae-related hepatitis in MP pneumonia pediatric patients: a predictive model construction and assessment.

BACKGROUND: A predictive model for risk of Mycoplasma pneumoniae (MP)-related hepatitis in MP pneumonia pediatric patients can improve treatment selection and therapeutic effect. However, currently, no predictive model is available. METHODS: Three hundred seventy-four pneumonia pediatric patients with/without serologically-confirmed MP infection and ninety-three health controls were enrolled. Logistic regressions were performed to identify the determinant variables and develop predictive model. Predictive performance and optimal diagnostic threshold were evaluated using area under the receiver operating characteristic curve (AUROC). Stratification analysis by age and MP-IgM titer was used to optimize model's clinical utility. An external validation set, including 84 MP pneumonia pediatric patients, was used to verify the predictive efficiency. After univariate analysis to screen significant variables, monocyte count (MO), erythrocyte distribution width (RDW) and platelet count (PLT) were identified as independent predictors in multivariate analysis. RESULTS: We constructed MRP model: MO [^109/L] × 4 + RDW [%] - PLT [^109/L] × 0.01. MRP achieved an AUROC of 0.754 and the sensitivity and specificity at cut-off value 10.44 were 71.72 and 61.00 %, respectively in predicting MP-related hepatitis from MP pneumonia. These results were verified by the external validation set, whereas it merely achieved an AUROC of 0.540 in pneumonia without MP infection. The AUROC of MRP was 0.812 and 0.787 in infants and toddlers (0-36 months) and low MP-IgM titer subgroup (1:160-1:320), respectively. It can achieve an AUROC of 0.804 in infants and toddler with low MP-IgM titer subgroup. CONCLUSIONS: MRP is an effective predictive model for risk of MP-related hepatitis in MP pneumonia pediatric patients, especially infants and toddlers with low MP-IgM titer.

Identification of an exosomal long non-coding RNAs panel for predicting recurrence risk in patients with colorectal cancer.

Recurrence is a major cause of cancer-related deaths in colorectal cancer (CRC) patients, but the current strategies are limited to predict this clinical behavior. Our aim is to develop a recurrence prediction model based on long non-coding RNAs (lncRNAs) in exosomes of serum to improve the prediction accuracy. In discovery phase, 11 lncRNAs were found to be associated with CRC recurrence in tissues using high-throughput lncRNAs microarray and reverse transcription quantitative real-time PCR. And, 9 of them were correlated with their expression levels of serum exosomes. In training phase, a model based on 5-exosomal lncRNAs (exolncRNAs) panel was constructed, and showed high distinguish capability for recurrent CRC patients. ROC showed the panel was superior to serum CEA and CA19-9 in prediction of CRC recurrence. In both training and test sets, high-risk patients defined by the 5-exolncRNAs panel had poor recurrence free and overall survival. And, COX model showed it was an independent factor for CRC prognosis. Moreover, there was a significant relationship in detection of 5-exolncRNAs between plasma samples and paired serum samples. In summary, the 5-exolncRNAs panel robustly stratifies CRC patients' risk of recurrence, enabling more accurate prediction of prognosis.