Duolu Li

MicroRNA-1 (miR-1) inhibits gastric cancer cell proliferation and migration by targeting MET

MicroRNAs (miRs) are short endogenous non-coding RNAs that act as posttranscriptional regulatory factors of gene expression. Downregulation of miR-1 has been reported in gastric cancer; however, the mechanisms underlying its functions via target genes in gastric cancer remain largely unknown. The purpose of this study was to investigate the mechanism by which miR-1 inhibits gastric cancer cell proliferation and migration. The effects of miR-1 on gastric cancer cell proliferation and migration were determined by MTT and wound-healing assays. Cell protein expression of the miR-1 target gene MET was analyzed by Western blotting. Finally, MET expression was evaluated by immunohistochemistry in a stomach tumor tissue microarray (TMA). Ectopic expression of miR-1 inhibited proliferation and migration in both AGS and SGC-7901 gastric cancer cell lines. miR-1 directly targets the MET gene and downregulates its expression. MET siRNA also inhibited proliferation and migration in both cell lines. Immunohistochemistry revealed significantly higher MET expression levels in gastric cancer tissues compared with matched adjacent non-cancer tissues. These findings indicate that the miR-1/MET pathway is a potential therapeutic target due to its crucial role in gastric cancer cell proliferation and migration.

Cyclin-dependent kinase 11p110 (CDK11p110) is crucial for human breast cancer cell proliferation and growth

Cyclin-dependent kinases (CDKs) play important roles in the development of many types of cancers by binding with their paired cyclins. However, the function of CDK11 larger protein isomer, CDK11p110, in the tumorigenesis of human breast cancer remains unclear. In the present study, we explored the effects and molecular mechanisms of CDK11p110 in the proliferation and growth of breast cancer cells by determining the expression of CDK11p110 in breast tumor tissues and examining the phenotypic changes of breast cancer cells after CDK11p110 knockdown. We found that CDK11p110 was highly expressed in breast tumor tissues and cell lines. Tissue microarray analysis showed that elevated CDK11p110 expression in breast cancer tissues significantly correlated with poor differentiation, and was also associated with advanced TNM stage and poor clinical prognosis for breast cancer patients. In vitro knockdown of CDK11p110 by siRNA significantly inhibited cell growth and migration, and dramatically induced apoptosis in breast cancer cells. Flow cytometry demonstrated that cells were markedly arrested in G1 phase of the cell cycle after CDK11p110 downregulation. These findings suggest that CDK11p110 is critical for the proliferation and growth of breast cancer cells, which highlights CDK11p110 may be a promising therapeutic target for the treatment of breast cancer.

Ammonia-induced energy disorders interfere with bilirubin metabolism in hepatocytes.

Hyperammonemia and jaundice are the most common clinical symptoms of hepatic failure. Decreasing the level of ammonia in the blood is often accompanied by a reduction in bilirubin in patients with hepatic failure. Previous studies have shown that hyperammonemia can cause bilirubin metabolism disorders, however it is unclear exactly how hyperammonemia interferes with bilirubin metabolism in hepatocytes. The purpose of the current study was to determine the mechanism or mechanisms by which hyperammonemia interferes with bilirubin metabolism in hepatocytes. Cell viability and apoptosis were analyzed in primary hepatocytes that had been exposed to ammonium chloride. Mitochondrial morphology and permeability were observed and analyzed, intermediates of the tricarboxylic acid (TCA) cycle were determined and changes in the expression of enzymes related to bilirubin metabolism were analyzed after ammonia exposure. Hyperammonemia inhibited cell growth, induced apoptosis, damaged the mitochondria and hindered the TCA cycle in hepatocytes. This led to a reduction in energy synthesis, eventually affecting the expression of enzymes related to bilirubin metabolism, which then caused further problems with bilirubin metabolism. These effects were significant, but could be reversed with the addition of adenosine triphosphate (ATP). This study demonstrates that ammonia can cause problems with bilirubin metabolism by interfering with energy synthesis.

Association between the TPH1 A218C polymorphism and antidepressant response: evidence from an updated ethnicity, antidepressant-specific, and ethnicity-antidepressant interaction meta-analysis.

Background Several studies have investigated the potential association between genetic polymorphisms of tryptophan hydroxylase 1 (TPH1) and antidepressant response. However, the results are inconsistent and inconclusive. Our aim was to assess the association of the TPH1 A218C polymorphism (rs1800532) with antidepressant response using ethnicity, antidepressant-specific, and ethnicity–antidepressant interactions in an updated meta-analysis. Patients and methods Data were collected from the related literature published before December 2013 from MEDLINE and EMBASE databases. The meta-analysis was stratified by ethnicity, antidepressants, and ethnicity–antidepressant interaction, and was carried out using a random-effects model as appropriate using the Stata Statistical Package (version 11.0). Results A total of 12 individual studies and the STAR*D study were identified in the current study, among which six studies and the STAR*D study (White part) reported on the TPH1 A218C polymorphism and antidepressant response in a White population, with 2035 cases, and six studies and the STAR*D study (Asian part) were carried out in an Asian population, with 707 cases. In terms of the classes of antidepressants, eight studies and the STAR*D study explored this relationship using selective serotonin reuptake inhibitors (SSRIs) and four studies used other/mixed antidepressants. We found that the TPH1 A218C genotype was not significantly associated with antidepressant response either in all populations or in White and Asian populations. Moreover, the results did not change according to an ethnicity–antidepressant interaction model either in White populations using SSRIs or other/mixed antidepressants or in Asian populations. Conclusion The TPH1 A218C polymorphism may not be associated with antidepressant response either in an ethnicity, antidepressant-specific population or in an ethnicity–antidepressant interaction model.

Specific expression of human interferon-gamma controls hepatitis B virus replication in vitro in secreting hepatitis B surface antigen hepatocytes.

Interferon-gamma (IFN-γ) has been reported to have antiviral activity against Hepatitis B virus (HBV) and to suppress HBV replication noncytolytically in vivo. Since systemic administration of IFN-γ may cause severe adverse effects, studies of the effects of liver-specific IFN-γ expression from adenoviral vectors in vivo have been investigated. In this study, a novel strategy has been described that drives specific expression of human IFN-γ in HBsAg-secreting hepatocytes. A bicistronic expression vector has been developed, pcDNA3.1-HBV antisense S gene-HCV core protein gene-HCV internal ribosome entry sites (IRES)-IFN-γ (pcDNA-SCIγ), by inserting four DNA fragments into pcDNA3.1. Tight modulation of HCV IRES-dependent translation by the HCV core protein was achieved using an antisense RNA technique with a bicistronic expression vector. HepG2 cells and HepG2.2.15 cells stably expressing HBV were transduced with pcDNA-SCIγ to test the responsiveness of IFN-γ to HBsAg expression. Gene transfer resulted in a low background and a 30-fold induction of IFN-γ expression from pcDNA-SCIγ in a cell-specific fashion. Hepatocyte-specific IFN-γ expression controlled effectively HBV replication in HBsAg-secreting HepG2.2.15 cells without cell toxicity.

-141C insertion/deletion polymorphism of the dopamine D2 receptor gene is associated with schizophrenia in Chinese Han population: Evidence from an ethnic group-specific meta-analysis.

Accumulate evidence has implicated dopamine D2 receptor gene polymorphisms in the etiology of schizophrenia. A single nucleotide polymorphism, −141C insertion/deletion (Ins/Del) (rs1799732), in the promoter region of the dopamine D2 receptor gene has been linked to schizophrenia; however, the data are inconclusive. This study investigated whether the −141C polymorphism is associated with the risk of schizophrenia in different ethnic groups by performing a meta‐analysis. A total of 24 case–control studies examining the association between −141C Ins/Del polymorphism and schizophrenia were identified according to established inclusion criteria. Significant association was revealed between −141C Ins/Del polymorphism and schizophrenia risk in dominant genetic model (Ins/Ins + Ins/Del versus Del/Del) (odds ratio = 0.33, 95% confidence interval = 0.14–0.81, z = 2.41, P = 0.02) in Chinese Han but not in Caucasian, Japanese or India populations. Our results indicate that −141C Ins/Del polymorphism might be a susceptibility factor for schizophrenia in Chinese Han population.

BTG3 Overexpression Suppresses the Proliferation and Invasion in Epithelial Ovarian Cancer Cell by Regulating AKT/GSK3β/β-Catenin Signaling

Epithelial ovarian cancer (EOC) is the leading cause of cancer-related death among all the gynecological malignancies of the female genital system, and its incidence and mortality rates continue to rise. B-cell translocation gene 3 (BTG3) plays an important role in the occurrence and development of numerous cancers. However, the role of BTG3 in EOC remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of BTG3 in EOC. We found that BTG3 protein expression was significantly lower in human EOC cell lines. Next, BTG3 upregulation by transfection with pcDNA3.1-BTG inhibited cell proliferation and invasion but promoted cell apoptosis in 2 human EOC cell lines, SKOV-3 and HO-8910 cells. In addition, BTG3 knockdown by small interfering RNA promoted cell proliferation and invasion, but inhibited cell apoptosis in 2 human EOC cell lines, SKOV-3 and HO-8910 cells. Importantly, several proteins, including phosphorylation serine/threonine kinase (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β), and β-catenin, were markedly decreased by BTG3 upregulation, whereas increased by BTG3 knockdown. Taken together, the results of our study suggest that BTG3 overexpression could inhibit cell proliferation and invasion and promotes cell apoptosis in EOC cell, possibly by regulating the AKT/GSK3β/β-catenin signaling pathway, providing novel insights into the treatment of EOC through BTG3 overexpression.