Wnt/ß-catenin signaling is associated with epithelial-mesenchymal transformation (EMT), which serves an important role in hepatocellular carcinoma (HCC) invasion and metastasis. Frankincense and myrrh (FM) are antitumor agents commonly used in clinical practice. The present study aimed to investigate the effect and mechanism of water extract of FM on the progression of liver cancer cells. FM was applied to study its effects on HCC cell proliferation. Cell migration and invasion were evaluated by wound healing and Transwell assays. In addition, western blot was used to study the protein levels associated with EMT and Wnt/ß-catenin signaling. The nuclear translocation of ß-catenin was detected by immunofluorescence assay. A non-toxic dose of FM significantly inhibited invasion and metastasis of liver cancer cells. Furthermore, FM promoted expression of EMT marker E-cadherin, while decreasing expression of vimentin and N-cadherin. Finally, the protein and the nuclear staining levels of Disheveled 2 and ß-catenin were both suppressed by water extract of FM. The water extract of FM inhibited the migration and invasion of liver cancer cells and inhibited EMT by suppressing activation of the Wnt/ß-catenin signaling pathway.
Liver tumor-initiating cells (T-ICs) contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. In the present study, our finding shows that miR-96 is upregulated in liver T-ICs. Functional studies revealed that forced miR-96 promotes liver T-ICs self-renewal and tumorigenesis. Conversely, knockdown miR-96 inhibits liver T-ICs self-renewal and tumorigenesis. Mechanistically, miR-96 downregulates TP53INP1 via its mRNA 3'UTR in liver T-ICs. Furthermore, the miR-96 expression determines the responses of hepatoma cells to sorafenib treatment. Analysis of patient cohorts and patient-derived xenografts (PDXs) further demonstrate that the miR-96 may predict sorafenib benefits in HCC patients. Our findings revealed the crucial role of the miR-96 in liver T-ICs expansion and sorafenib response, rendering miR-96 as an optimal target for the prevention and intervention of HCC.
BACKGROUND: Recent GWAS-associated studies reported that single nucleotide polymorphisms (SNPs) in ABCB1, TGFß1, XRCC1 genes were associated with hepatitis A virus (HAV) infection, and variants of APOA4 and APOE genes were associated with and hepatitis E virus (HEV) infection in US population. However, the associations of these loci with HAV or HEV infection in Chinese Han population remain unclear. METHODS: A total of 3082 Chinese Han persons were included in this study. Anti-HAV IgG and anti-HEV IgG were detected by enzyme-linked immunosorbent assay (ELISA). Genotypes in ABCB1, TGFß1, XRCC1, APOA4 and APOE SNPs were determined by TaqMan MGB technology. RESULTS: In Chinese Han population, rs1045642 C to T variation in ABCB1 was significantly associated with the decreased risk of HAV infection (P < 0.05). However, the effect direction was different with the previous US study. Rs1001581 A to G variation in XRCC1, which was not identified in US population, was significantly associated with the protection against HAV infection in our samples (P < 0.05). In addition, our results suggested that rs7412 C to T variation in APOE was significantly associated with lower risk of HEV infection in males (adjusted OR < 1.0, P < 0.05) but not in females. CONCLUSIONS: ABCB1 and XRCC1 genes variants are significantly associated with the protection against HAV infection. Additionally, Chinese Han males with rs7412 C to T variation in APOE gene are less prone to be infected by HEV.
Genetic Predisposition to Disease , Hepatitis A virus , Hepatitis A/epidemiology , Hepatitis A/genetics , Hepatitis E virus , Hepatitis E/epidemiology , Hepatitis E/genetics , Adult , Aged , China/epidemiology , Female , Gene Expression Regulation , Genome-Wide Association Study , Genotype , Hepatitis A/immunology , Hepatitis A virus/immunology , Hepatitis E/immunology , Hepatitis E virus/immunology , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Polymorphism, Single Nucleotide , Population Surveillance , Seroepidemiologic Studies
1,3,7-Trihydroxyxanthone is a compound isolated from Polygalae Radix, a medicinal herb frequently applied for treatment of psychiatric disordres with symptoms of forgetfulness and depression in ancient China. In current research, this compound was applied onto rat astrocyte primary cultures in exploring the action mechanisms of 1,3,7-trihydroxyxanthone on regulating synthesis of neurotrophic factors. It was found that 1,3,7-trihydroxyxanthone could significantly stimulate the expression of NGF and BDNF in dose-dependent manners: the stimulation was both in mRNA and protein levels. Furthermore, 1,3,7-trihydroxyxanthone might fulfill this effect by regulating critical enzymes, such as plasminogen, tissue plasminogen activator, neuroserpin and tissue inhibitor of metalloproteinases in metabolic pathway of neurotrophic factors. Besides, inhibitors of cAMP- and ERK-dependent pathways, which implied the possible signaling pathway, could reverse this inducing effect. These results might support the potentiality of 1,3,7-trihydroxyxanthone in drug development in treating psychiatric disorders.
Astrocytes/metabolism , Cyclic AMP/metabolism , Drugs, Chinese Herbal/pharmacology , MAP Kinase Signaling System/drug effects , Nerve Growth Factors/metabolism , Xanthones/pharmacology , Animals , Astrocytes/drug effects , Cells, Cultured , Metabolic Networks and Pathways/drug effects , Nerve Growth Factors/genetics , Phytotherapy , Plasminogen Activator Inhibitor 1/metabolism , Proteolysis/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Tissue Plasminogen Activator/metabolism , Xanthones/chemistry
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-associated mortality worldwide, particularly in China. MicroRNAs (miRs) serve important roles in the pathogenesis of HCC. The present study investigated the function of miR-1271 in HCC. The miR-1271 levels were analyzed by quantitative reverse transcription polymerase chain reaction. Cells growth was examined by MTT assay. Bioinformatics algorithms from TargetScanHuman were used to predict the target genes of miR-1271. The protein level was assayed by western blotting. miR-1271 demonstrated a lower expression level in HCC tissues. Upregulation of miR-1271 suppressed the growth of HepG-2 and Huh-7 cells and induced apoptosis of cells. Forkhead box Q1 (FOXQ1) was targeted by miR-1271. In conclusion, miR-1271 is a novel tumor suppressor that inhibits HCC proliferation and induces cellular apoptosis by targeting FOXQ1 in HCC. The results of the present study may provide a novel therapeutic target of HCC.
