MiR-876-5p acts as an inhibitor in hepatocellular carcinoma progression by targeting DNMT3A

Hepatocellular carcinoma (HCC) is one of the biggest challenges that human beings faced with in 21st century. Previous researches have revealed that miRNAs can serve as regulators in various cancers. MiR-876-5p, a member of miRNA family, has been studied in lung cancer for its anti-oncogenic function. However, the exact function of it is not reported in HCC. Our study aims to find out the effects of miR-876-5p expression on HCC progression. Two HCC cells were chosen to do functional assays after miR-876-5p expression was detected in cell lines by qRT-PCR. HepG2 cell was transfected with miR-876-5p mimics, whereas LM3 cell was transfected with miR-876-5p inhibitors. Next, cell activities of these two indicated cells were analyzed by means of MTT assay, colony forming assay, transwell migration assay and western blot analysis. Consequently, we found that miR-876-5p could inhibit both cell proliferation and metastasis. Moreover, we found out a target gene (DNMT3A) of miR-876-5p by performing bioinformatics analysis, dual luciferase reporter assay and biotin-avidin pull-down assay. Finally, rescue assays were carried out in HepG2 cells. We found that DNMT3A could reverse miR-876-5p mimics-induced inhibition. Therefore, we concluded that miR-876-5p suppressed hepatocellular carcinoma progression by targeting DNMT3A.     

MicroRNAs in hepatic pathophysiology

MicroRNAs (miRNAs) are a group of small non‐coding RNAs that range in length from 20 to 25 nucleotides. MicroRNAs are specific for multiple cellular functions, including cell generation, differentiation, multiplication, carcinogenesis, and apoptosis. Many researchers have recently reported that the aberrant expression of miRNAs in hepatic tissue was related to the pathogenesis of liver disease, including viral hepatitis, hepatocellular carcinoma, and fatty liver disease. Multiple studies have proposed that an analysis of circulating miRNAs may be useful for diagnosing etiologies or staging the progression of liver disease, as well as for therapeutic purposes, for example, nucleic acid therapy. This review summarizes and discusses recent advances in the knowledge of miRNAs for chronic liver diseases, with special interest in viral hepatitis, liver fibrosis, and biomarkers.     

Leptin as a potential therapeutic target for breast cancer prevention and treatment

Background: Hepatocellular carcinoma (HCC) develops most often in a background of chronic inflammatory liver injury from viral infection or alcohol use. Most HCCs are diagnosed at a stage at which surgical resection is not feasible. Even in patients receiving surgery rates of recurrence and metastasis remain high. There are few effective HCC therapies and hence a need for novel, rational approaches to treatment. Platelet derived growth factor receptor-α (PDGFR-α) is involved in tumor angiogenesis and maintenance of the tumor microenvironment and has been implicated in development and metastasis of HCC. Objective: To examine PDGFR-α as a target for therapy of HCC and explore opportunities and strategies for PDGFR-α inhibition. Methods: A review of relevant literature. Results/conclusions: Targeted inhibition of PDGFR-α is a rational strategy for prevention and therapy of HCC.     

Malignant liver tumours

The liver is commonly affected by both primary and metastatic malignancy. The surgical management of liver tumours must be carefully considered to ensure good oncological outcomes and to avoid serious complications of liver surgery. Primary tumours of the liver include hepatocellular carcinoma and cholangiocarcinoma. The resectability of primary liver tumours is dependent on thorough preoperative staging. Primary liver tumours pose a major global health burden, particularly in Asia and in countries affected by epidemic viral hepatitis. Metastatic disease commonly affects the liver and often hepatic resection in such circumstances provides the best chance of prolonging life and disease free survival. This review discusses recent advances, in addition to the epidemiology, diagnosis and management of both primary and secondary liver tumours.     

Disruption of beta-catenin pathway or genomic instability define two distinct categories of liver cancer in transgenic mice

BACKGROUND & AIMS: Human liver cancer can be divided into 2 categories that are characterized by activation of beta-catenin and genomic instability. Here we investigate whether similar categories exist among 5 transgenic models of liver cancer, including c-myc, transforming growth factor-alpha, E2F-1, c-myc/transforming growth factor-alpha, and c-myc/E2F-1 mice. METHODS: The random amplified polymorphic DNA method was used to assess the overall genomic instability, and chromosomal loci affected by genomic alterations were determined by microsatellite analysis. beta-Catenin mutations and deletions were analyzed by polymerase chain reaction and sequencing screening. Cellular localization of beta-catenin and expression of alpha-fetoprotein, a prognostic marker of hepatocellular carcinoma, were investigated by immunohistochemistry. RESULTS: Liver tumors from the transgenic mice could be divided into 2 broad categories characterized by extensive genomic instability (exemplified by the c-myc/transforming growth factor-alpha mouse) and activation of beta-catenin (exemplified by the c-myc/E2F-1 mouse). The c-myc/transforming growth factor-alpha tumors displayed extensive genomic instability with recurrent loss of heterozygosity at chromosomes 1, 2, 4, 6, 7, 9, 12, 14, and X and a low rate of beta-catenin activation. The genomic instability was evident from the early dysplastic stage and occurred concomitantly with increased expression of alpha-fetoprotein. The c-myc/E2F-1 tumors were characterized by a high frequency of beta-catenin activation in the presence of a relatively stable genome and low alpha-fetoprotein levels. CONCLUSIONS: We have identified 2 prototype experimental models, i.e., c-myc/transforming growth factor-alpha and c-myc/E2F-1 mice, for the 2 categories of human hepatocellular carcinoma characterized by genomic instability and beta-catenin activation, respectively. These mouse models will assist in the elucidation of the molecular basis of human hepatocellular carcinoma.     

自然杀伤细胞抗肝癌的研究新进展

肝癌是最常见的恶性肿瘤之一,预后差,复发率高。免疫治疗已成为继手术、放疗、化疗后的第四种治疗模式,其中自然杀伤细胞可以在细胞、分子及基因水平抑制肿瘤转移及复发,在肝癌的免疫治疗中起关键性作用,在开展新的治疗模式以及提高肝癌患者生活质量方面具有很广阔的应用前景。