Fuyan Wang

Bio: Fuyan Wang is an academic researcher from Ningbo University. The author has contributed to research in topics: Diabetes mellitus & Cancer. The author has an hindex of 8, co-authored 15 publications receiving 196 citations.

Dipeptidyl peptidase-4 inhibitors and cancer risk in patients with type 2 diabetes: a meta-analysis of randomized clinical trials.

Abstract: Some recent studies have suggested that the use of dipeptidyl peptidase-4 inhibitors (DPP4i) is associated with cancer development. However, some other studies suggest no such association. The aim of the present study was to evaluate the effect of DPP4i on the risk of developing cancers. The electronic databases PubMed, Medline, EMBASE, Web of Science and Cochrane Library and the clinical trial registry were searched for published and unpublished randomized clinical trials on humans. Eligible studies were RCTs conducted in patients with type 2 diabetes mellitus, comparing DPP4i with a placebo or other active drugs. A total of 72 trials with 35,768 and 33,319 patients enrolled for DPP4i and the comparison drugs, respectively. Overall, no significant associations were detected between the use of DPP4i and cancer development, in comparison with the use of other active drugs or placebo. The results were consistent across pre-defined subgroups stratified by type of DPP4i, type of cancer, drug for comparison, trial duration, or baseline characteristics. The results of this meta-analysis suggest that patients with type 2 diabetes treated with DPP4i do not have a higher risk of developing cancers than patients treated with a placebo or other drugs.

Prevalence of Pre-Diabetes and Its Associated Risk Factors in Rural Areas of Ningbo, China.

Abstract: Objective: The aims of the study were to investigate the prevalence of pre-diabetes and explore its associated risk factors in rural areas of Ningbo, China. Methods: A cross-sectional survey was conducted with 4583 adult residents in rural areas of Ningbo, China between March and May 2013. The survey used a multi-stage, stratified, cluster sampling method. Data collected included demographics and medical history, anthropometric measurements, blood pressure, blood lipid, and plasma glucose. After at least 10 h of overnight fasting, participants underwent an oral glucose tolerance test (OGTT) to identify pre-diabetes. Univariate and multivariate logistic regression analyses were used to evaluate the associated risk factors for pre-diabetes, and to estimate the effect of interaction between the factors. Results: There were 1307 survey participants having pre-diabetes (28.52%) and the age-standardized prevalence was 30.53%. Multivariate logistic regression results showed that overweight/obesity, hypertension, and higher triglycerides were the risk factors for developing pre-diabetes. There were positive interactions between overweight/obesity and triglycerides, and also between hypertension and triglycerides on the multiplicative scale, suggesting that they synergistically influenced the development of pre-diabetes. Conclusions: The rural areas in Ningbo had a high prevalence of pre-diabetes. Overweight and obesity, hypertension, and elevated triglycerides were the major risk factors. There is a need of early intervention for preventing pre-diabetes.

High glucose induces epithelial‑mesenchymal transition and results in the migration and invasion of colorectal cancer cells

Abstract: Diabetes mellitus (DM) is associated with an increased risk of colorectal cancer (CRC). Hyperglycemia, a chronic abnormality in diabetes, is an independent predictor of cancer-associated mortality in CRC. However, the underlying biological mechanism of hyperglycemia in CRC cells is largely unknown. In the present study, HCT-116 and HT-29 cell proliferation, apoptosis, migration and invasion were assessed. In addition, the expression of epithelial (E)-cadherin, vimentin and high-mobility group A protein 2 (HMGA2) were assessed using western blotting. The results demonstrated that high glucose (HG; 30 mmol/l) caused CRC cells to lose their epithelial morphology, with a decrease in E-cadherin and an increase in vimentin, suggesting epithelial-mesenchymal transition (EMT). Furthermore, HG significantly enhanced the cell migration and invasion of CRC cells and the expression of HMGA2. Transfection with HMGA2 small interfering RNA reversed the HG-induced changes to CRC cells. In addition, HG promoted CRC cell proliferation and suppressed apoptosis. The results of the present study suggest that hyperglycemia promotes EMT, proliferation, migration and invasion in CRC cells and may provide novel insights into the link between HG and CRC.

A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

Abstract: Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.

The epigenetics of epithelial-mesenchymal plasticity in cancer

Abstract: Epithelial-mesenchymal transitions (EMTs) are a key requirement for cancer cells to metastasize and colonize in a new environment. Epithelial-mesenchymal plasticity is mediated by master transcription factors and is also subject to complex epigenetic regulation. This Review outlines our current understanding of the interactions between EMT-inducing transcription factors and epigenetic modulators during cancer progression and the therapeutic implications of exploiting this intricate regulatory process. During the course of malignant cancer progression, neoplastic cells undergo dynamic and reversible transitions between multiple phenotypic states, the extremes of which are defined by the expression of epithelial and mesenchymal phenotypes. This plasticity is enabled by underlying shifts in epigenetic regulation. A small cohort of pleiotropically acting transcription factors is widely recognized to effect these shifts by controlling the expression of a constituency of key target genes. These master regulators depend on complex epigenetic regulatory mechanisms, notably the induction of changes in the modifications of chromatin-associated histones, in order to achieve the widespread changes in gene expression observed during epithelial-mesenchymal transitions (EMTs). These associations indicate that an understanding of the functional interactions between such EMT-inducing transcription factors and the modulators of chromatin configuration will provide crucial insights into the fundamental mechanisms underlying cancer progression and may, in the longer term, generate new diagnostic and therapeutic modalities for treating high-grade malignancies.

Fueling the fire: emerging role of the hexosamine biosynthetic pathway in cancer

Abstract: Altered metabolism and deregulated cellular energetics are now considered a hallmark of all cancers. Glucose, glutamine, fatty acids, and amino acids are the primary drivers of tumor growth and act as substrates for the hexosamine biosynthetic pathway (HBP). The HBP culminates in the production of an amino sugar uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) that, along with other charged nucleotide sugars, serves as the basis for biosynthesis of glycoproteins and other glycoconjugates. These nutrient-driven post-translational modifications are highly altered in cancer and regulate protein functions in various cancer-associated processes. In this review, we discuss recent progress in understanding the mechanistic relationship between the HBP and cancer.

STAT3, stem cells, cancer stem cells and p63.

Abstract: Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor with many important functions in the biology of normal and transformed cells. Its regulation is highly complex as it is involved in signaling pathways in many different cell types and under a wide variety of conditions. Besides other functions, STAT3 is an important regulator of normal stem cells and cancer stem cells. p63 which is a member of the p53 protein family is also involved in these functions and is both physically and functionally connected with STAT3. This review summarizes STAT3 function and regulation, its role in stem cell and cancer stem cell properties and highlights recent reports about its relationship to p63.

The ERK Pathway: Molecular Mechanisms and Treatment of Depression

Abstract: Major depressive disorder is a chronic debilitating mental illness. Its pathophysiology at cellular and molecular levels is incompletely understood. Increasing evidence supports a pivotal role of the mitogen-activated protein kinase (MAPK), in particular the extracellular signal-regulated kinase (ERK) subclass of MAPKs, in the pathogenesis, symptomatology, and treatment of depression. In humans and various chronic animal models of depression, the ERK signaling was significantly downregulated in the prefrontal cortex and hippocampus, two core areas implicated in depression. Inhibiting the ERK pathway in these areas caused depression-like behavior. A variety of antidepressants produced their behavioral effects in part via normalizing the downregulated ERK activity. In addition to ERK, the brain-derived neurotrophic factor (BDNF), an immediate upstream regulator of ERK, the cAMP response element-binding protein (CREB), a transcription factor downstream to ERK, and the MAPK phosphatase (MKP) are equally vulnerable to depression. While BDNF and CREB were reduced in their activity in the prefrontal cortex and hippocampus of depressed animals, MKP activity was enhanced in parallel. Chronic antidepressant treatment readily reversed these neurochemical changes. Thus, ERK signaling in the depression-implicated brain regions was disrupted during the development of depression, which contributes to the long-lasting and transcription-dependent neuroadaptations critical for enduring depression-like behavior and the therapeutic effect of antidepressants.