ABSTRACT
Objective: lncRNA HAND2 antisense RNA 1 (HAND2-AS1) is consistently well recognized to suppress multiple tumors, while its function was uncertified in liver cancer. Materials and Methods: qRT-PCR analysis and TCGA database discovered the expression in liver cancer. CCK-8 and Transwell migration assay demonstrated the impact of HAND2-AS1 on cell proliferation and migration. Bioinformatic analysis and luciferase reporter assay were utilized to monitor the binding between HAND2-AS1 or SOCS5 mRNA and miR-3118. The function of SOCS5 on inactivating the JAK-STAT pathway was confirmed through Western blot assays. Rescue experiments unmasked that HAND2-AS1-mediated SOCS5 affected cell proliferation and migration through the JAK-STAT pathway in liver cancer. Results: The authors discovered the downregulated HAND2-AS1 in liver cancer cells. HAND2-AS1 augmentation apparently impaired the capacity of liver cancer viability, proliferation, and migration. Cytoplasmic HAND2-AS1 directly bound to miR-3118 and released SOCS5, leading to upregulation of SOCS5. Next, the negative regulator role of SOCS5 in the adjusting JAK-STAT pathway was reconfirmed in this study. Conclusions: HAND2-AS1 enhanced inactivation of the JAK-STAT pathway through sponging miR-3118 and facilitating SOCS5 to retard cell proliferation and migration in liver cancer.
Subject(s)
Janus Kinases/metabolism , RNA, Long Noncoding/metabolism , STAT3 Transcription Factor/metabolism , Suppressor of Cytokine Signaling Proteins/metabolism , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Suppressor of Cytokine Signaling Proteins/genetics , Transfection , Up-RegulationABSTRACT
BACKGROUND: The absent in melanoma 2 (AIM2), a cytosolic dsDNA inflammasome, can be activated by viral DNA to trigger caspase-1. Its role in immunopathology of chronic hepatitis B and C virus (HBV, HCV) infection is still largely unclear. In this study, the expression AIM2, and its downstream cytokines, caspase-1, IL-18 and IL-1ß, in liver tissue of patients with chronic hepatitis B and C (CHB, CHC) were investigated. METHODS: A total of 70 patients diagnosed with chronic hepatitis were enrolled, including 47 patients with CHB and 23 patients with CHC. A liver biopsy was taken from each patient, and immunohistochemistry was used to detect the expression of AIM2 and inflammatory factors caspase-1, IL-18, and IL-1ß in the biopsy specimens. The relationship between AIM2 expression and these inflammatory factors was analyzed. RESULTS: The expression of AIM2 in CHB patients (89.4 %) was significantly higher than in CHC patients (8.7 %), and among the CHB patients, the expression of AIM2 was significantly higher in the high HBV replication group (HBV DNA ≥ 1 × 10(5)copies/mL) than in the low HBV replication group (HBV DNA < 1 × 10(5)copies/mL). The expression of AIM2 was also correlated with HBV-associated inflammatory activity in CHB patients statistically. Additionally, AIM2 levels were positively correlated with the expression of caspase-1, IL-1ß and IL-18 in CHB patients, which implied that the AIM2 expression is directly correlated with the inflammatory activity associated with CHB. CONCLUSIONS: AIM2 upregulation may be a component of HBV immunopathology. The underlying mechanism and possible signal pathway warrant further study.
Subject(s)
DNA-Binding Proteins/analysis , Gene Expression Profiling , Hepatitis B, Chronic/pathology , Hepatitis C, Chronic/pathology , Inflammation/pathology , Liver/pathology , Adolescent , Adult , Biopsy , Female , Humans , Immunohistochemistry , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: Nicotinamide phosphoribosyl transferase (Nampt) plays a crucial role in tumorigenesis. The present study examines whether genetic polymorphisms of NAMPT are related to the risk of developing esophageal squamous cell carcinoma (ESCC). METHODS: A total of 810 subjects were enrolled in this study, including 405 ESCC patients and 405 healthy controls. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), genotypes at rs61330082, rs2505568 and rs9034 of NAMPT were identified. Haplotypes were constructed using PHASE software. Multivariate logistic regression models were used to evaluate the potentiating effects of the genotypes, alleles and haplotypes on the development of ESCC. RESULTS: The presence of genotypes CT and TT and allele T at rs61330082 was less frequent in ESCC cases than in controls (48.89% vs. 53.33%, P < 0.01, 95% CI: 0.33-0.68; 18.52% vs. 30.37%, P < 0.01, 95% CI: 0.22-0.50; 42.96% vs. 57.04%, P < 0.01, 95% CI: 0.38-0.61; respectively). No statistically significant differences existed in the distributions of genotypes or alleles at rs2505568 or rs9034 between ESCC cases and controls. Of five haplotypes constructed, haplotypes CTC, CTT and CAC were higher in ESCC cases (P < 0.01, OR = 1.57, 95% CI: 1.16-2.12; P = 0.04, OR = 1.72, 95% CI: 1.03-2.85; P < 0.01, OR = 3.39, 95% CI: 1.99-5.75; respectively) than in controls. CONCLUSION: Genetic polymorphisms of NAMPT, specifically genotype CC and allele C at rs61330082 as well as haplotypes CTC, CTT and CAC, were significantly correlated with ESCC susceptibility.
