Long Non-Coding RNA ANRIL Regulates Inflammatory Factor Expression in Ulcerative Colitis Via the miR-191-5p/SATB1 Axis.

Ulcerative colitis, an inflammatory bowel disease, manifests with symptoms such as abdominal pain, diarrhea, and mucopurulent feces. The long non-coding RNA (lncRNA) ANRIL exhibits significantly reduced expression in UC, yet its specific mechanism is unknown. This study revealed that ANRIL is involved in the progression of UC by inhibiting IL-6 and TNF-α via miR-191-5P/SATB1 axis. We found that in patients with UC, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly overexpressed in inflamed colon sites, whereas ANRIL was significantly under-expressed and associated with disease severity. The downregulation of ANRIL resulted in the increased expression of IL-6 and TNF-α in LPS-treated FHCs. ANRIL directly targeted miR-191-5p, thereby inhibiting its expression and augmenting SATB1 expression. Moreover, overexpression of miR-191-5p abolished ANRIL-mediated inhibition of IL-6 and TNF-α production. Dual luciferase reporter assays revealed the specific binding of miR-191-5p to ANRIL and SATB1. Furthermore, the downregulation of ANRIL promoted DSS-induced colitis in mice. Together, we provide evidence that ANRIL plays a critical role in regulating IL-6 and TNF-α expression in UC by modulating the miR-191-5p/SATB1 axis. Our study provides novel insights into progression and molecular therapeutic strategies in UC.

Comparison of Different Machine Models Based on Multi-Phase Computed Tomography Radiomic Analysis to Differentiate Parotid Basal Cell Adenoma From Pleomorphic Adenoma.

Objective: This study explored the value of different radiomic models based on multiphase computed tomography in differentiating parotid pleomorphic adenoma (PA) and basal cell tumor (BCA) concerning the predominant phase and the optimal radiomic model. Methods: This study enrolled 173 patients with pathologically confirmed parotid tumors (training cohort: n=121; testing cohort: n=52). Radiomic features were extracted from the nonenhanced, arterial, venous, and delayed phases CT images. After dimensionality reduction and screening, logistic regression (LR), K-nearest neighbor (KNN) and support vector machine (SVM) were applied to develop radiomic models. The optimal radiomic model was selected by using ROC curve analysis. Univariate and multivariable logistic regression was performed to analyze clinical-radiological characteristics and to identify variables for developing a clinical model. A combined model was constructed by integrating clinical and radiomic features. Model performances were assessed by ROC curve analysis. Results: A total of 1036 radiomic features were extracted from each phase of CT images. Sixteen radiomic features were considered valuable by dimensionality reduction and screening. Among radiomic models, the SVM model of the arterial and delayed phases showed superior predictive efficiency and robustness (AUC, training cohort: 0.822, 0.838; testing cohort: 0.752, 0.751). The discriminatory capability of the combined model was the best (AUC, training cohort: 0.885; testing cohort: 0.834). Conclusions: The diagnostic performance of the arterial and delayed phases contributed more than other phases. However, the combined model demonstrated excellent ability to distinguish BCA from PA, which may provide a non-invasive and efficient method for clinical decision-making.

Aquaporin 9 inhibits hepatocellular carcinoma through up-regulating FOXO1 expression.

Aquaporin 9 (AQP9) is the main aquaglyceroporin in the liver. Few studies have been performed regarding the role of AQP9 in liver cancer. Here we report AQP9 expression and function in liver cancer. We found that AQP9 mRNA and protein levels were reduced in human hepatocellular cancer compared to the para-tumor normal liver tissues. Human hepatoma cell line SMMC7721 expressed low basal levels of AQP9. When AQP9 was overexpressed in SMMC7721 cell line, cell proliferation was inhibited due to cell cycle arrest at G1 phase and increased apoptosis. At the molecular level, AQP9 overexpression decreased the protein levels of phosphatidylinositol-3-kinase (PI3K), leading to reduced phosphorylation of Akt. Subsequently, the protein levels of forkhead box protein O1 (FOXO1) were increased, resulting in down-regulation of proliferating cell nuclear antigen (PCNA) expression and up-regulation of caspase-3 expression. AQP9 overexpression inhibited growth of subcutaneously xenografted liver tumors in nude mice. These findings suggest that AQP9 expression is down-regulated in liver cancer compared to the normal liver tissue and restoration of AQP9 expression can inhibit development of liver cancer.

Aquaporin 9 is down-regulated in hepatocellular carcinoma and its over-expression suppresses hepatoma cell invasion through inhibiting epithelial-to-mesenchymal transition.

Aquaporin 9 (AQP9) is the main aquaglyceroporin in the liver. Few studies have been performed regarding the role of AQP9 in hepatocellular carcinoma (HCC). Here, we report the expression and function of AQP9 in HCC tissues and cell lines. We found that AQP9 mRNA and protein levels were down-regulated in HCC tissues and human hepatoma cell lines compared to the para-cancer normal liver tissues and normal hepatocyte line, respectively. In a human HCC SMMC-7721 cell line, over-expression of AQP9 suppressed cell invasion in vitro and xenograft tumor growth in vivo. AQP9 over-expression increased the expression of E-cadherin and decreased the expression of N-cadherin in SMMC-7721 cells and xenografted tumors, which was correlated with decreased levels of phosphoinositide 3-kinase (PI3K) and p-Akt. Conversely, using siRNA to knock down AQP9 over-expression could reverse the phenotype caused by AQP9 over-expression. Our findings suggest that AQP9 is down-regulated in hepatocellular carcinoma and its over-expression suppresses hepatoma cell invasion through inhibiting epithelial-to-mesenchymal transition.

Expression and clinical significance of aquaglyceroporins in human hepatocellular carcinoma.

Aquaglyceroporins (AQPs) are a subset of the aquaporin family, and are permeable to water and glycerol. The aim of the present study was to determine the expression and clinical significance of three AQPs, AQP3, 7 and 9 in hepatocellular carcinoma (HCC). Fresh HCC and adjacent non­tumorous liver tissues were collected from 68 patients diagnosed with HCC. The expression levels of AQP3, 7 and 9 were detected by reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemical analysis. The association between the expression of AQPs and clinicopathological parameters of HCC were investigated. Compared with non­tumorous liver tissue, HCC tissues exhibited a significant (P<0.05) increase in the expression of AQP3 and a concomitant reduction in the expression levels of AQP7 and AQP9, at both the mRNA and protein levels. Immunohistochemistry revealed that AQP9 was dominantly localized on the plasma membrane of hepatocytes, while AQP3 and AQP7 exhibited a predominantly cytoplasmic and nuclear distribution. High expression of AQP3 was significantly (P<0.05) associated with low expression levels of AQP7 and AQP9. High expression of AQP3 was correlated with tumor grade (P=0.017), tumor stage (P=0.010) and lymphatic metastasis (P=0.031). Low expression of AQP7 was correlated with tumor grade (P=0.043). AQP3 was upregulated, and AQP7 and AQP9 were downregulated in HCC. A high expression of AQP3 and low expression of AQP7 was significantly associated with the aggressive features of HCC.

FOXO1-mediated epigenetic modifications are involved in the insulin-mediated repression of hepatocyte aquaporin 9 expression.

Aquaporin (AQP) 9 transports glycerol and water, and belongs to the aquaglyceroporin subfamily. Insulin acts as a negative regulator of AQP9, and FOXO1 has the ability to mediate the regulatory effects of insulin on target gene expression. The aim of the present study was to determine whether insulin­induced repression of AQP9 involved an epigenetic mechanism. HepG2 human hepatocyte cells were treated with 500 µM insulin for different durations. AQP9 mRNA expression levels were determined by quantitative polymerase chain reaction (qPCR), and histone H3 acetylation, phosphorylation and methylation at the insulin responsive element (IRE) of the AQP9 promoter was assessed using chromatin immunoprecipitation coupled with qPCR. The effects of lentiviral FOXO1 overexpression on AQP9 expression levels and H3 modifications at the AQP9 promoter were also determined. The insulin treatment resulted in a significant and time­dependent reduction in AQP9 mRNA expression levels in HepG2 cells, as compared with untreated cells (P<0.05). In the insulin­treated cells, the levels of H3 acetylation and phosphorylation were significantly reduced (P<0.05), but the level of H3 methylation was increased. Enforced expression of FOXO1 increased AQP9 mRNA and protein expression levels in HepG2 cells. Furthermore, FOXO1 overexpression promoted H3 acetylation and phosphorylation, and reduced H3 methylation at the IRE locus of the AQP9 promoter. These data provide, to the best of our knowledge, the first evidence that insulin­induced transcriptional suppression of AQP9 expression in hepatocytes involves FOXO1­mediated H3 modifications at the IRE locus in the promoter.