LINC00667 Promotes Progression of Esophageal Cancer Cells by Regulating miR-200b-3p/SLC2A3 Axis.

BACKGROUND: Recently, more and more evidence indicated that the long non-coding RNA was strictly related to the occurrence and progression of human cancers, including esophageal cancer (EC). We observed that LINC00667 was increased in EC, but the function of LINC00667 was unclear. Therefore, the function and potential molecular mechanism of LINC00667 in the progression of EC need to be further studied. METHODS: Quantitative real-time PCR was used to investigate the levels of LINC00667, miR-200b-3p, and SLC2A3. The levels of protein involved in cell cycle, cell apoptosis, epithelial-mesenchymal transition, as well as SLC2A3 were quantitatived by western blot. The role of LINC00667 in the proliferative, migratory and invasive capabilities of EC cells were measured by cell counting kit-8 assay, EdU assay, flow cytometry assay, wound healing assay and transwell assay, respectively. Interaction between LINC00667 and miR-200b-3p or miR-200b-3p and SLC2A3 were confirmed using a luciferase reporter assay. RESULTS: In this work, we found that LINC00667 expression was up-regulated in EC cell lines, and LINC00667 knockdown inhibited cell proliferation, migration, and invasion in EC cells. In addition, it showed that LINC00667 functioned as competitive endogenous RNA for miR-200b-3p by the DIANA-LncBase database. Moreover, we used targetscan online software to predict SLC2A3 as a target gene of miR-200b-3p. Subsequently, rescue experiments confirmed that knocking out SLC2A3 could reverse the inhibitory effect of miR-200b-3p on EC cells transfected with sh-LINC00667. CONCLUSION: Herein, we revealed the novel mechanism of LINC00667 on regulating metastasis-related gene by sponge regulatory axis during EC metastasis. Our results demonstrated that LINC00667 plays a critical role in metastatic EC by mediating sponge regulatory axis miR-200b-3p/SLC2A3. To explore function of LINC00667/miR-200b-3p/SLC2A3 axis may provide an informative biomarker of malignancy and a highly selective anti-EC therapeutic target.

LINC01980 stimulates the progression of hepatocellular carcinoma via downregulating caspase 9.

PURPOSE: To uncover the role of LINC01980 in aggravating the progression of hepatocellular carcinoma (HCC) via targeting caspase 9. METHODS: The expression levels of LINC01980 and caspase 9 in HCC tissues and paracancer tissues were determined by qRT-PCR. The prognostic potentials of LINC01980 and caspase 9 in HCC were assessed by Kaplan-Meier method. The regulatory effects of LINC01980 and caspase 9 on the viability, clonality and apoptosis of Huh7 and Hep3B cells were examined. Finally, the interaction between LINC01980 and caspase 9 was evaluated by performing dual-luciferase reporter gene assay and rescue experiments. RESULTS: LINC01980 was upregulated in HCC tissues and cells. High level of LINC01980 indicated worse prognosis in HCC patients. Knockdown of LINC01980 could attenuate viability and clonality, but induced apoptosis in Huh7 and Hep3B cells. Caspase 9 was downregulated in HCC, and its high level predicted a better prognosis in HCC patients. Overexpression of caspase 9 achieved the same regulatory effects as LINC01980 knockdown on HCC cells. Caspase 9 was the downstream target for LINC01980, and its level was negatively regulated by LINC01980. In HCC, LINC01980 regulated HCC cell behaviors by downregulating caspase 9. CONCLUSIONS: Upregulation of LINC01980 in HCC predicts a poor prognosis. LINC01980 aggravates the progression of HCC via downregulating caspase 9.

Association between circulating inflammatory molecules and alcoholic liver disease in men.

The association between alcoholic liver disease (ALD) and the inflammatory response remains controversial. The aim of this study was to explore this association between ALD and inflammation. We enrolled 214 male participants, who were divided into three age-matched groups: ALD (n = 135), chronic alcohol ingestion without ALD (non-ALD; n = 42), and control (n = 37). The BMI was significantly higher in the ALD group than in the non-ALD and control groups (all P = 0.000). Further, the constituent ratio of the liver inflammatory level was significantly higher in the ALD group than in the non-ALD and control groups (P = 0.002 and P = 0.000, respectively). In addition, the median serum ALT, AST, and GGT levels were significantly higher in the ALD group than in the control group (P = 0.023, P = 0.008, and P = 0.000, respectively); these levels were also significantly higher in the ALD group than in the non-ALD group (P = 0.013, P = 0.010, and P = 0.000, respectively). The median serum CRP level was significantly higher in the ALD group than in the non-ALD and control groups (P = 0.006 and P = 0.000, respectively). Further, the median serum TNF-α level was significantly lower in the ALD group than in the non-ALD and control groups (P = 0.004 and P = 0.000, respectively). The median serum sOX40L and HSP70 levels were significantly lower in the ALD group than in the control group (P = 0.008 and P = 0.018, respectively). In addition, the ALT, AST, and GGT levels were positively correlated with the CRP level (r = 0.211, P = 0.002; r = 0.220, P = 0.001 and r = 0.295, P = 0.000, respectively), and the GGT level was negatively correlated with the TNF-α (r = -0.225, P = 0.001), sOX40L (r = -0.165, P = 0.016), and HSP70 levels (r = -0.178, P = 0.009). Further, the Cr level was negatively correlated with the IL-10 level (r = -0.166, P = 0.015). Logistic regression analysis verified that the BMI (OR  =  1.637, 95%CI: 1.374-1.951, P  =  0.000) and GGT level were significantly higher (OR  =  1.039, 95%CI: 1.020-1.059, P  =  0.000) and that the TNF-α (OR  =  0.998, 95%CI: 0.996-1.000, P  =  0.030) and HSP70 levels were significantly lower (OR  =  1.017, 95%CI: 1.003-1.031, P  =  0.029) in the ALD group than in the non-ALD group. Further, the moderate-to-severe ALD patients had a significantly higher serum CRP level (Or =   1.349, 95%CI: 1.066-1.702, P  =  0.013) and significantly lower HSP60 (OR  =  0.965, 95%CI: 0.938-0.993, P  =  0.014) and HSP70 levels (OR  =  0.978, 95%CI: 0.962-0.995, P  =  0.010) than the mild ALD patients. These results suggest that ALD patients may present with obesity, liver damage, and an imbalanced inflammatory immune response, mainly manifesting as decreased levels of immune inflammatory cytokines. In addition, they suggest that certain liver and kidney function parameters and ALD severity are either positively or negatively correlated with certain inflammatory cytokines. Hence, ALD patients may be at increased risks of obesity- and inflammation-related diseases. Accordingly, to control the inflammatory response, preventative measures for patients with this disease should include weight control and protection of liver and kidney function.

Risk Factors Associated With Increased Carotid Intima-Media Thickness in a Male Population With Chronic Alcohol Consumption: A Prospective Observational Study.

Previous studies have reported a relationship between alcohol consumption and carotid intima-media thickness (CIMT). However, the exact associations between different severities of CIMT and dyslipidemia, dyslipoproteinemia, inflammatory immune markers, and oxidative markers associated with chronic alcohol consumption remain unknown. The aim of this study was to explore whether there are associations between different severities of CIMT and dyslipidemia, dyslipoproteinemia, inflammatory immune markers, and oxidative markers associated with chronic alcohol consumption. We enrolled 173 males with chronic alcohol consumption and categorized them into 2 groups: 104 chronic alcohol consumers with normal CIMT (group A) and 69 chronic alcohol consumers with increased CIMT (group B). Nonparametric statistics showed that age, body mass index (BMI), and serum TC, TG, Apo A1, and ApoB levels were significantly higher in group B than in group A (P = 0.002, 0.019, 0.021, 0.023, 0.001, and 0.001, respectively). Additionally, tumor necrosis factor alpha (TNFα) and HSP70 serum levels were significantly lower in group B than in group A (P = 0.023 and 0.017, respectively). A binary logistic regression analysis showed that age (OR: 1.077, 95% CI: 1.024-1.13, P = 0.004), ApoB (OR: 6.828, 95% CI: 1.506-30.956, P = 0.013), and TNF-α (OR: 0.999, 95% CI: 0.998-1.00) were independent risk factors associated with CIMT. The present study demonstrated that age, ApoB, and TNFα are independent risk factors associated with CIMT. Thus, older subjects with increased serum ApoB levels are more likely to present with increased CIMT, suggesting that age and ApoB promote such thickening and that TNFα downregulation might play a protective role against the progression of subclinical atherosclerosis in subjects with chronic alcohol consumption.

Influence of H. pylori CagA Coupled with Alcohol Consumption on Cytokine Profiles in Men.

The aim of this study was to evaluate the effect of Helicobacter pylori (H pylori) cytotoxin-associated gene A (CagA) coupled with chronic alcohol ingestion on cytokine profiles.A total of 215 male subjects were divided into the following 4 groups: 130 alcohol H pylori CagA-negative consumers (CagA-) (group A), 50 alcohol H pylori CagA-positive consumers (CagA+) (group B), 24 nonalcohol H pylori CagA-negative consumers (group C), and 11 nonalcohol H pylori CagA-positive consumers (group D). The serum CagA, C-reactive protein (CRP), interleukin (IL)-6, IL-10, E-selectin, adiponectin (ADP), and tumor necrosis factor-α (TNF-α) levels were measured through enzyme-linked immunosorbent assays (ELISAs).After adjusting for age and mean alcohol drinking history, a multivariable linear regression analysis revealed that the mean daily alcohol consumption, IL-6, TNF-α, and ADP levels were significantly increased with increases in the serum CagA concentrations (P = 0.008, P = 0.000, P = 0.000, and P = 0.006, respectively). The serum IL-6 and IL-10 levels of group A were significantly lower than those of group B (all P = 0.000). Furthermore, the serum IL-6 and IL-10 levels of groups A and C were significantly lower than those of group D (all P = 0.000), and the serum IL-6 and IL-10 levels of group C were significantly lower than those of group B (all P = 0.000). The serum ADP and E-selectin levels of groups B and D were significantly higher than those of group A (P = 0.000). The serum ADP levels of group B were significantly higher than those of group C (P = 0.000), and the serum ADP and E-selectin levels of group C were significantly lower than those of group D (P = 0.000 and P = 0.005, respectively). Finally, the serum TNF-α levels of groups B, C, and D were significantly higher than those of group A (all P = 0.000), and the serum TNF-α levels of group C were significantly higher than those of group D (P = 0.005).In conclusion, H pylori CagA may result in significantly higher levels of several inflammatory markers in both alcohol consumers and nonalcohol consumers. However, chronic alcohol ingestion coupled with H pylori CagA positivity does not result in significant changes in cytokine profiles.

Causes of Thickening of Carotid Intima-Media Thickness in Patients With Alcoholic Liver Disease: A Prospective Observational Study.

Several studies have reported the relationship between alcoholic liver disease (ALD) and carotid intima-media thickness (CIMT). Few studies, however, have investigated the causes of CIMT thickening in patients with ALD. The authors explored the causes of CIMT thickening in patients with ALD. The authors enrolled 152 patients who were stratified into groups: nonthickening CIMT with ALD (group A); thickening CIMT with ALD (group B); nonthickening CIMT without ALD (group C); and thickening CIMT without ALD (group D). The CIMT was significantly different between patients with and without ALD (χ 2= 3.875, P = 0.049). The patients in groups A, B, and C were significantly younger than group D (P = 0.001, 0.036, and 0.001, respectively). The body mass indexes (BMI) in groups A and B were significantly higher than in group C (P = 0.000 and 0.007, respectively). The blood glucose levels in groups B and D were significantly higher than in group C (P = 0.016 and 0.018, respectively). The blood uric acid levels in group B were significantly higher than in groups A, C, and D (P = 0.009, 0.000, and 0.003, respectively). The blood uric acid in group A was significantly higher than in group C (P = 0.002). The serum total cholesterol (TC) levels of patients in group B were significantly higher than in groups A and C (P = 0.027 and 0.000, respectively) and the serum TC level in group A was significantly higher than in group C (P = 0.048). The serum triglyceride (TG) levels in groups A and B were significantly higher than in group C (P = 0.027 and 0.000, respectively). The serum of very low-density lipoprotein (VLDL) levels in group B were significantly higher than in group C (P = 0.000). Although a comparison of the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) serum levels among the 4 groups indicated no changes. The serum LDL levels in group B were significantly higher than in group A (P = 0.008). No significant differences were observed among the groups with respect to serum homocysteine, C-reactive protein (CRP), interleukin-6 (IL-6), malondialdehyde (MDA), superoxide dismutase (SOD), soluble OX40 ligand (sOX40L), or heat shock protein (HSP) 60 or 70. Alcoholic liver disease may result in CIMT thickening. Carotid intima-media thickness is associated with age and metabolic factors in patients with ALD. In addition, ALD might promote the premature occurrence of CIMT thickening. The thickening of carotid artery intima thickness, however, is not associated with cytokine profiles, oxidative balance, or immune responses in patients with ALD.

Effect of H. pylori Infection on Cytokine Profiles and Oxidative Balance in Subjects with Chronic Alcohol Ingestion.

Different amounts of ingested alcohol can have distinct effects on the human body. However, there is limited research on chronic alcohol consumption with Helicobacter pylori infection. We sought to investigate the relationship between the cytokine profile, oxidative balance and H. pylori infection in subjects with chronic alcohol consumption. A total of 142 subjects were divided into three groups: 59 subjects with chronic alcohol ingestion and H. pylori infection (group A); 53 subjects with chronic alcohol ingestion without H. pylori infection (group B); and 30 control subjects (group C). The serum levels of CagA, interleukin (IL)-10, E-selectin, TNF-α, malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by enzyme-linked immunosorbent assay (ELISA). We found that the ages and serum H. pylori CagA levels among the three groups, as well as both the mean drinking age and the mean daily alcohol consumption between groups A and B, were matched and comparable. Comparing the BMIs among the three groups, the BMI differences were found to be statistically significant (F=3.921, P<0.05). Compared with group C, the BMIs in groups A and B were significantly higher (P<0.001 and P<0.01, respectively); however, the BMI differences between group A and group B were not statistically significant (P>0.05). Additionally, no differences in the serum CagA levels were found in comparisons among the groups (all P>0.05). The serum IL-10 and E-selectin levels in group A were significantly lower than those in group B (serum IL-10: P<0.05; E-selectin: P<0.05). The serum IL-10 in group A was significantly higher than that in group C (P<0.01); the serum E-selectin levels in group A did not significantly differ compared with those in group C (P>0.05). Furthermore, the serum IL-10 and E-selectin levels in group B were significantly higher than those in group C (serum IL-10: P<0.001; E-selectin: P<0.05); however, the serum TNF-α levels did not differ among groups (all P>0.05). Although the serum levels of MDA and SOD in groups A and B were slightly lower than those in group C, there were no significant differences among groups (all P>0.05). In conclusion, we believe that H. pylori infection might cause a significant inhibition of certain cytokine profiles in subjects with chronic alcohol ingestion. Moreover, chronically ingested alcohol may exert an adjusted inflammatory effect, but there was no association between H. pylori infection, chronic alcohol consumption and oxidative balance.

Changes in tumor necrosis factor-α, heat shock protein 70, malondialdehyde, and superoxide dismutase in patients with different severities of alcoholic fatty liver disease: a prospective observational study.

The relationships among inflammation, oxidative balance, and the severity of alcoholic fatty liver disease (AFLD) remain unknown. The aim of this study is to explore the relationships among tumor necrosis factor alpha (TNF-α), heat shock protein 70 (HSP70), malondialdehyde (MDA), superoxide dismutase (SOD), and the severity of AFLD.From January 2012 to December 2013, 162 participants were enrolled in this study and divided into 4 groups: 44 cases of mild AFLD (group A), 55 cases of moderate-to-severe AFLD (group B), 44 cases of alcohol consumption without AFLD (group C), and 20 cases of no alcohol consumption without AFLD (group D). A cross-sectional study was conducted by detecting the serum levels of TNF-α, HSP70, MDA, and SOD by enzyme-linked immunosorbent assay.The median serum levels of TNF-α and HSP70 among the 4 groups were statistically significant (P = 0.000 and 0.001, respectively). The median serum levels of TNF-α in groups A and B were significantly lower than in group C (P = 0.002 and 0.000, respectively), and the median serum level of TNF-α in group B was significantly lower than in group D (P = 0.023). In addition, the median serum level of HSP70 in group B was significantly lower than in groups A and C (P = 0.002 and 0.000, respectively), and the median serum level of HSP70 in group C was significantly higher than in group D (P = 0.044). However, the median serum level of MDA in group B was significantly lower than only group C (P = 0.008).Chronic alcohol ingestion without AFLD may result in a significant increase in the circulation of certain inflammatory markers; the severity of AFLD is associated with circulating inflammatory markers, and moderate-to-severe AFLD may result in a more significant reduction of these markers. However, moderate-to-severe AFLD may also result in a significant downregulation of oxidative stress products.