Comprehensive Analysis of TRIM Family Genes in Hepatitis Virus B-Related Hepatoma Carcinoma.

Background: As significant components of E3 ligases, the tripartite motif (TRIM) proteins participate in various biological processes and facilitate the development of several diseases. Nevertheless, the correlations of TIRMs with hepatitis B virus (HBV)-positive hepatoma carcinoma (HCC) are not well elaborated. Methods: The expression profile of TRIM genes in HBV-associated HCC and related clinical information were extracted from the Cancer Genome Atla (TCGA) database and the International Cancer Genome Consortium (ICGC) database. Dependent on the ConsensusPathDB and STRING databases, the gene ontology, Reactome pathways, and protein-protein interaction were assessed. Relied on TIMER 2.0 database, the relationship of the TRIMs with immune infiltration was investigated. Using multivariate analysis and Kaplan Meier analysis, the association between TRIM genes and the prognostic value was examined. Results: A total of 17 TRIM genes, including TRIM16, TRIM17, and TRIM31 with fold change no less than 1.5, were discovered to upregulate in HBV-associated HCC in both TCGA and ICGC cohorts. Relied on gene enrichment analysis, the identified TRIMs were observed to not only be related to the interferon and cytokine signaling but also linked to the adaptive immune system. Particularly, the co-expression patterns of identified TRIMs with other E3 ligase genes and many innate immune genes that are associated with Toll-like receptor signaling, apoptosis, and SUMOylation. Besides, some of identified TRIM expressions were also linked to the infiltration levels of T cells and B cells. Additionally, several TRIM genes were associated with various clinical factors and relevant to the poor survival of HBV-associated HCC. Conclusion: Our findings could deepen our understanding of TRIMs and their correlations with HBV-associated HCC. Furthermore, some of these TRIMs may be utilized as new prognostic markers of HBV-related HCC prognosis, or act as potential molecular targets for the disease.

Safety and Efficacy of Radiofrequency Ablation for Solitary Hepatocellular Carcinoma (3-5 cm): a Propensity Score Matching Cohort Study.

BACKGROUND: We aim to investigate the safety and efficacy of radiofrequency ablation in the treatment of solitary hepatocellular carcinoma (3-5 cm) in comparison with surgical resection. METHODS: Included in this study were 388 patients with primary and solitary hepatocellular carcinoma, of whom 196 patients underwent surgical resection and the other 192 patients received radiofrequency ablation. Clinicopathological characteristics, prognosis, post-treatment complications, hospital stay, and financial expenditures between the two groups were compared retrospectively. RESULTS: The result of propensity score matching and subgroup analysis showed that the 1-, 3-, and 5-year overall survival and disease-free survival were comparable in patients with tumors of 3-4 cm in diameter between surgical resection and radiofrequency ablation groups. However, when the tumor size exceeded 4 cm in diameter, surgical resection exhibited a superior long-term prognosis compared with radiofrequency ablation. Nevertheless, hepatectomy was associated with high occurrences of postoperative complications, long hospital stay, and high hospitalization cost as compared with radiofrequency ablation. Further analysis of the relationship between tumor size and pathological features of hepatocellular carcinoma showed that tumors larger than 4 cm were positively correlated with a high rate of microvascular invasion and satellite nodule formation. CONCLUSION: For solitary hepatocellular carcinoma of 3-4 cm in diameter, radiofrequency ablation could achieve a comparable prognosis with a low incidence of post-treatment complications and low hospitalization costs, while surgical resection is recommended for solitary hepatocellular carcinoma tumors of 4-5 cm in diameter when long-term prognosis is considered.

Klf4 inhibits tumor growth and metastasis by targeting microRNA-31 in human hepatocellular carcinoma.

MicroRNAs (miRNAs or miRs) are short, endogenous non-coding RNA molecules, demonstrating abnormal expression in cancer initiation and progression. In this study, we profiled 18 differentially regulated miRNAs, including miRNA­31, using miRNA array. Kruppel (or Krüppel)-like factor 4 (Klf4) is a transcription factor and putative tumor suppressor. Both were found to be significantly downregulated in liver cancer tissues and cells. However, little is known about the correlation between Klf4 and miRNA­31 in hepatocellular carcinoma (HCC). The mRNA expression of Klf4 was decreased and inversely associated with the clinical stage, T classification and hepatitis B in patients with HCC, while the expression of miR­31 was lower (r=0.326, P=0.018). Using cell counting kit 8 (CCK8) and Transwell migration assays, we found that Klf4 and miR­31 inhibited the proliferation and metastasis of liver cancer cells. Moreover, we demonstrated that Klf4 directly binds to the promoter of miR­31 and activates its transcription. In vitro experiments confirmed that Klf4 regulated miR­31 and thereby inhibited HCC cell growth and metastasis. Taken together, our findings indicate that Klf4 directly regulates miR­31 in HCC. Thus, miR-31 may serve as a potential diagnostic marker and therapeutic target in HCC.

Down-regulation of Krüppel-like factor-4 by microRNA-135a-5p promotes proliferation and metastasis in hepatocellular carcinoma by transforming growth factor-ß1.

Krüppel-like Factor-4 (KLF4) is a zinc finger transcription factor which plays an important role in cell cycle, proliferation and apoptosis. In Hepatocellular Carcinoma (HCC), the function of KLF4 has been characterized as tumor suppressor. However, the mechanism remains largely unknown. In this study, we demonstrated that TGF-ß1 down-regulated KLF4 by activating miR-135a-5p. MiR-135a-5p promoted proliferation and metastasis in HCC cells by direct targeting KLF4 both in vitro and in vivo. In addition, miR-135a-5p expression was up-regulated in clinical HCC tissues, and was inversely correlated with the expression of KLF4. Taken together, our data indicated that TGF-ß1 down-regulated KLF4 by activating miR-135a-5p, promoting proliferation and metastasis in HCC.