Hongguang Li

Aberrant Expression of CCAT1 Regulated by c-Myc Predicts the Prognosis of Hepatocellular Carcinoma

BACKGROUND CCAT1 has been reported to be linked with pathogenesis of malignancies including colon cancer and gastric cancer. However, the regulatory effect of CCAT1 in hepatocellular carcinoma (HCC) remains unclear. The purpose of this research was to identify any role of CCAT1 in the progression of HCC. MATERIALS AND METHODS Real time-PCR was performed to test the relative expression of CCAT1 in HCC tissues. A computation screen of CCAT1 promoter was conducted to search for transcription-factor-binding sites. The association of c-Myc with CCAT1 promoter in vivo was tested by Pearson correlation analysis and chromatin immunoprecipitation assay. Additionally, Kaplan-Meier analysis and Cox proportional hazards analyses were performed. RESULTS c-Myc directly binds to the E-box element in the promoter region of CCAT, and when ectopically expressed increases promoter activity and expression of CCAT1. Moreover, Kaplan-Meier analysis demonstrated that the patients with low expression of CCAT1 demonstrated better overall and relapse-free survival compared with the high expression group. Cox proportional hazards analyses showed that CCAT1 expression was an independent prognostic factor for HCC patients. CONCLUSIONS The findings demonstrated CCAT1, acting as a potential biomarker in predicting the prognosis of HCC, is regulated by c-Myc.

Low Expression of miR-448 Induces EMT and Promotes Invasion by Regulating ROCK2 in Hepatocellular Carcinoma.

Background/Aims: miR-448 has been reported to exhibit abnormal expression in hepatocellular carcinoma (HCC), however, the essential role of miR-448 in HCC progression is still unclear. Methods: real-time PCR was used to detect the expression of miRNAs and candidate genes in HCC samples (n=117). miR-448 mimics and inhibitor were tansfected in human HCC cells. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter assay. The markers of EMT were detected by using Western blot. Results: miR-448 was decreased in HCC samples and associated with HCC development. Inhibition of miR-448 significantly promoted cell invasion, while the effect of miR-448 up-regulation was reverse. miR-448 could regulate ROCK2 in hepatocellular carcinoma. Knockdown of ROCK2 expression partially reversed the effect of miR-448 inhibitor. Abnormal expression of miR-448 could regulate the markers of epithelial-mesenchymal transition (EMT). Conclusions: miR-448 may contribute to the progression of HCC via regulating ROCK2 expression.

Identification of hepatocellular carcinoma-associated hub genes and pathways by integrated microarray analysis.

Aims and Background Hepatocellular carcinoma (HCC) is a dismal malignancy associated with multiple molecular changes. The purpose of this study was to identify the differentially expressed genes and analyze the biological processes related to HCC. Methods and Study Design Datasets of HCC were obtained from the NCBI Gene Expression Omnibus. Integrated analysis of differentially expressed genes was performed using the INMEX program. Then Gene Ontology enrichment analyses and pathway analysis were performed based on the Gene Ontology website and Kyoto Encyclopedia of Genes and Genomes. A protein-protein interaction network was constructed using the Cytoscape software; the netwerk served to find hub genes for HCC. Real-time RT-PCR was used to validate the microarray data for hub genes. Results We identified 273 genes that were differentially expressed in HCC. Gene Ontology enrichment analyses revealed response to cadmium ion, cellular response to cadmium ion, and cellular response to zinc ion for these genes. Pathway analysis showed that significant pathways included fatty acid metabolism, butanoate metabolism, and PPAR signaling pathway. The protein-protein interaction network indicated that CDH1, ECHS1, ACAA1, MT2A, and MYC were important genes which participated in many interactions. Experimental validation of the role of four upregulated genes (ECHS1, ACAA1, MT2A and MYC) in the progression of HCC was carried out. Conclusions Our study displayed genes that were consistently differentially expressed in HCC. The biological pathways and protein-protein interaction networks associated with those genes were also identified. We predicted that CDH1, ECHS1, ACAA1, MT2A, and MYC might be target genes for diagnosing HCC.

MiR-1180 promoted the proliferation of hepatocellular carcinoma cells by repressing TNIP2 expression

MicroRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional regulatory function, playing crucial roles in cancer development and progression of hepatocellular carcinoma (HCC). Previous studies have indicated that miR-1180 was implicated in diverse biological processes. However, the underlying mechanism of miR-1180 in HCC has not been intensively investigated. In this study, we aimed to investigate the role of miR-1180 and its target genes in HCC. We found that miR-1180 expression was significantly increased in HCC cells and clinical tissues compared with their corresponding controls. Overexpression of miR-1180 promoted cell proliferation in HCC cell line HepG2. TNFAIP3 interacting protein 2 (TNIP2), a potential target gene of miR-1180, and were validated by a luciferase assay. Further studies revealed that miR-1180 regulated cell proliferation of HCC by directly suppressing TNIP2 expression and the knockdown of TNIP2 expression reversed the effect of miR-1180-in on HCC cell proliferation. In summary, our data indicated that miR-1180 might act as a tumor promoter by targeting TNIP2 during development of HCC.

Interaction Between Polymorphisms of IFN-γ and MICA Correlated with Hepatocellular Carcinoma

Background We explored the relationship of interferon--γ (IFN-γ) and MHC class-I chain related gene A (MICA) genes polymorphisms with hepatocellular carcinoma (HCC) risk, and tried to determine whether the interaction existed between these two genes polymorphisms on the basis of HCC. Material/Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect the genotypes of the 3 single-nucleotide polymorphisms (SNPs) and to analyze the correlation of each SNP with HCC susceptibility in 120 HCC patients and 124 healthy people. The association strength between the 3 SNPs and HCC is represented with odds ratio (OR) and 95% confidence interval (95% CI). Hardy-Weinberg equilibrium (HWE) was tested by χ2 test in the control group. Results GG genotype of IFN-γ rs2069727 polymorphism had apparently different distributions in case and control groups (P<0.05), and might confer increased risk of HCC (OR=3.40, 95%CI=1.23–9.38). Analysis of MICA rs2596542 polymorphism also yielded the same result (OR=2.90, 95%CI=1.10–7.67), as did their risk alleles. Specifically, the interaction between rs2596542 and rs2069705 polymorphisms increased the HCC risk by 1.41 times and between rs2596542 and rs2069727 polymorphisms the increased risk of HCC by 5.56 times. Conclusions IFN-γ rs2069727 and MICA rs2596542 polymorphisms may be related to the incidence of HCC. Interaction exists between the polymorphisms of IFN-γ and MICA, which may increase risk of HCC.

Less Aggressive Surgical Procedure for Treatment of Solid Pseudopapillary Tumor: Limited Experience from a Single Institute

OBJECTIVES To evaluate the clinical characteristics and radiological features of solid pseudopapillary tumor (SPT) and assess surgical therapy strategy. METHODS A retrospective review was performed in 62 patients pathologically confirmed of SPT treated between 2003 and 2014. The clinical features, radiological examinations and surgical strategies were analyzed. RESULTS 56 females and 6 males were included in this study, mean age was 26 years old (range: 8-66 years old) with mean size of the tumor was 7.2 cm (range: 3-15 cm), and most tumor were commonly located in the head of pancreas (n = 29). Among all the cases, 3 patients had liver metastasis and underwent resection of SPT and liver metastasis. Furthermore, we performed 29 cases of local tumor excision; other patients underwent pancreaticoduodenectomy, middle pancreatectomy, middle pancreatectomy with splenectomy, distal pancreatectomy with spleen preservation, distal pancreatectomy with splenectomy and duodenum-preserving pancreatic head resection. No patient suffered from lymph node metastases. After median follow-up of 46 months (range: 2-135 months), no mortality or local recurrence or distant metastasis was found. CONCLUSIONS Solid pseudopapillary tumor is a latent malignant tumor with excellent prognosis. If feasible, less aggressive resection without regular lymphadenectomy is recommended for treatment of patients with SPT.

Common Variants of the Prostaglandin-Endoperoxide Synthase 2 Gene and Hepatocellular Carcinoma Susceptibility

AbstractHepatocellular carcinoma (HCC) is a heterogeneous disease with substantial genetic constitution. Previous work has evaluated the effect of prostaglandin-endoperoxide synthase 2 (PTGS2) variants (−765G/C, −1195A/G, and +8473T/C) on the development of HCC, but the conclusions are inconsistent. We conducted a meta-analysis in this work. Data from 7 case–control studies were combined to assess the association between PTGS2 variants and HCC. The risk of HCC (OR and 95% CI) was estimated using either the fixed- or the random-effects model according to the Q test. No significant association was identified for −765G/C and +8473T/C. However, we identified a significantly decreased risk in relation to the GG genotype of −1195A/G (OR = 0.70, 95% CI = 0.50–0.98 for GG versus AA). We also observed a similar decrease (OR = 0.47, 95% CI = 0.23–0.95 for GG versus AA) in Caucasian samples. Variant −1195A/G in the promoter PTGS2 may protect against the malignant progression of HCC. This significant association suggests that −1195A/G could be used as a biomarker of HCC.

Significant Association Between Adiponutrin and Hepatocellular Carcinoma Risk.

AbstractADPN I148M polymorphism has been consistently reported to play a role in liver-associated diseases, such as alcoholic liver disease, chronic hepatitis C, and liver fat and fibrosis in nonalcoholic fatty liver disease. This significant association was also indicated in a series of hepatocellular carcinoma (HCC) studies, where the significance may be affected due to the small sample sizes. The aim of this study was to reexamine the ADPN-HCC association by use of meta-analysis. Biweekly computer-based literature searches plus manual screening were undertaken in an effort to identify all studies that met the predefined inclusion criteria. The Mantel–Haenszel method was selected to estimate risk effects (odds ratio [OR] and 95% confidence interval [CI]). To examine reliability of the pooled risk effects, we additionally performed sensitivity analysis and publication bias tests. Ten studies (1335 HCC patients and 2927 HCC-free controls) were identified for the meta-analysis. We found significantly increased risk of HCC attributable to presence of ADPN I148M polymorphism, with the highest risk associated with the M/M genotype under the recessive model of inheritance (OR = 2.23, 95% CI = 1.87–2.67, between-study heterogeneity: P = 0.468). The significant increase persisted in Caucasian and African when data were stratified by ethnicity. Subgroup analysis according to source of controls revealed similar risk effects. Our meta-analysis indicates that I148M polymorphism in the ADPN gene may independently contribute to the progression of HCC irrespective of the etiologies.