ORCID Profile
0000-0003-1223-4595
Current Organisations
The Chinese University of Hong Kong
,
The Chinese University of Hong Kong Faculty of Medicine
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Publisher: American Association for Cancer Research (AACR)
Date: 15-02-2015
DOI: 10.1158/0008-5472.CAN-14-1301
Abstract: Chromatin remodeling has emerged as a hallmark of gastric cancer, but the regulation of chromatin regulators other than genetic change is unknown. Helicobacter pylori causes epigenetic dysregulation to promote gastric carcinogenesis, but the roles and functions of microRNAs (miRNA) in this multistage cascade are not fully explored. In this study, miRNA expression in preneoplastic and neoplastic lesions in murine stomachs induced by H. pylori and N-methyl-N-nitrosourea (MNU) was profiled by miRNA expression array. miR-490-3p exhibited progressive downregulation in gastritis, intestinal metaplasia, and adenocarcinoma during H. pylori and MNU-induced gastric carcinogenesis. Significant downregulation of miR-490-3p was confirmed in human gastric cancer tissues in which its regulatory region was found to be hypermethylated. miR-490-3p exerted growth- and metastasis-suppressive effects on gastric cancer cells through directly targeting SMARCD1, a SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex subunit. Knockdown of SMARCD1 significantly attenuated the protumorigenic effects of miR-490-3p inhibitor, whereas enforced expression of SMARCD1 promoted in vitro and in vivo oncogenic phenotypes of gastric cancer cells. SMARCD1 was markedly upregulated in gastric cancer in which its high expression was associated with shortened patients' survival independent of TNM staging. In conclusion, hypermethylation-mediated silencing of miR-490-3p reactivates SMARCD1 to confer malignant phenotypes, mechanistically linking H. pylori, chromatin remodeling, and gastric carcinogenesis. Cancer Res 75(4) 754–65. ©2014 AACR.
Publisher: Elsevier BV
Date: 11-2018
Abstract: Cancer-related genes are under intense evolutionary pressure. We conjectured that gene size is an important determinant of lification propensity for oncogenes and thus cancer susceptibility and therefore could be subject to natural selection. Gene information, including size and genomic locations, of all protein-coding genes were downloaded from Ensembl (release 87). Quantification of gene lification was based on Genomic Identification of Significant Targets in Cancer scores obtained from available The Cancer Genome Atlas studies. Oncogenes are larger in size as compared with non-cancer genes (mean size: 92.1 kb versus 61.4 kb P < 0.0001) in the human genome, which is contributed by both increased total exon size (mean size: 4.6 kb versus 3.4 kb P < 0.0001) and higher intronic content (mean %: 84.8 versus 78.0 P < 0.01). Such non-random size distribution and intronic composition are conserved in mouse and Drosophila (all P < 0.0001). Stratification by gene age indicated that young oncogenes have been subject to a stronger evolutionary pressure for gene expansion than their non-cancer counterparts. Pan-cancer analysis demonstrated that larger oncogenes were lified to a lesser extent. Tumor-suppressor genes also moved toward small oncogenes in the course of evolution. Oncogenes expand in size whereas tumor-suppressor genes move closer to small oncogenes in the course of evolution to withstand oncogenic somatic lification. Our findings have shed new light on the previously unappreciated influence of gene size on oncogene lification and elucidated how cancers have shaped our genome to its present configuration.
Publisher: Wiley
Date: 28-02-2018
DOI: 10.1002/PATH.5033
Abstract: Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori-infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacological ablation of autophagy in mouse and cell line models of H. pylori infection. Here, we showed that H. pylori inhibited lysosomal function and thereby promoted the accumulation of autophagosomes in gastric epithelial cells. Importantly, inhibiting autophagosome formation by pharmacological inhibitors or genetic ablation of BECN1 or ATG5 reduced H. pylori intracellular survival, whereas inhibition of lysosomal functions exerted an opposite effect. Further experiments demonstrated that H. pylori inhibited lysosomal acidification and the retrograde trafficking of mannose-6-phosphate receptors, both of which are known to positively regulate lysosomal function. We conclude that H. pylori subverts autophagy into a pro-survival mechanism through inhibition of lysosomal clearance of autophagosomes. Disruption of autophagosome formation offers a novel strategy to reduce H. pylori colonization in human stomachs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Publisher: Oxford University Press (OUP)
Date: 12-01-2017
Publisher: CSIRO Publishing
Date: 2019
DOI: 10.1071/SR18223
Abstract: There is currently relatively little available information on subsoil phosphorus (P) use for crop production as a function of soil order. In this study, a rhizobox experiment was performed using subsoils of two reference soil groups, an Orthic Ferralsol and a Haplic Luvisol. To evaluate the immediate P uptake by wheat (Triticum aestivum L.) from different subsoil P pools during 14 days of growth, subsoil bands were spiked with KH2PO4 solution associated to Fe-hydroxide (33P-Fe), to Al-hydroxide (33P-Al), in free form (33P-OrthoP), or in trace amounts without any additional 31P (33P-NoP). At the beginning of the experiment, the soil water content was set at 75% of water-holding capacity, corresponding to an initial soil matric potential of −12 ± 1 kPa. During plant growth, soil moisture decreased in both soils, but soil matric potentials in both soils did not drop below field capacity (−33 kPa pF 2.5). The shoot dry weights of the Ferralsol were 1.2 to 1.8 times those of the Luvisol. Despite elevated soil P availability in the Luvisol, shoot P concentrations did not differ between the two soils. The amount of 33P taken up by the shoots from the oxide phases was 15% to 40% greater in the Ferralsol treatments than in those in the Luvisol treatments. It was concluded that the more favourable physical soil conditions facilitated 33P uptake from both oxidic phases from the Ferralsol subsoil relative to the Luvisol subsoil, despite better P phytoavailability in the latter.
Location: No location found
Location: Hong Kong
No related grants have been discovered for Maggie Haitian Wang.