ORCID Profile
0000-0002-4618-0719
Current Organisations
University of California, San Diego
,
The Chinese University of Hong Kong Faculty of Medicine
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Publisher: Springer Science and Business Media LLC
Date: 06-05-2022
DOI: 10.1038/S41388-022-02343-5
Abstract: Cancer-related genes have evolved specific genetic and genomic features to favor tumor suppression. Previously we reported that tumor suppressor genes (TSGs) acquired high promoter CpG dinucleotide frequencies during evolution to maintain high expression in normal tissues and resist cancer-specific downregulation. In this study, we investigated whether 3'untranslated regions (3'UTRs) of TSGs have evolved specific features to carry out similar functions. We found that 3'UTRs of TSGs, especially those involved in multiple histological types and pediatric cancers, are longer than those of non-cancer genes. 3'UTRs of TSGs also exhibit higher density of binding sites for RNA-binding proteins (RBPs), particularly those having high affinities to C-rich motifs. Both longer 3'UTR length and RBP binding sites enrichment are correlated with higher gene expression in normal tissues across tissue types. Moreover, both features together with the correlated N
Publisher: Springer Science and Business Media LLC
Date: 08-11-2017
DOI: 10.1038/NATURE24302
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: Oxford University Press (OUP)
Date: 12-01-2017
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1053/J.GASTRO.2018.04.028
Abstract: Colorectal cancer (CRC) development has been associated with increased proportions of Bacteroides fragilis and certain Streptococcus, Fusobacterium, and Peptostreptococcus species in the intestinal microbiota. We investigated associations between bacteremia from specific intestinal microbes and occurrence of CRC. We performed a retrospective study after collecting data on 13,096 adult patients (exposed group) in Hong Kong hospitalized with bacteremia (identified by blood culture test) without a previous diagnosis of cancer from January 1, 2006 through December 31, 2015. We collected data on intestinal microbes previously associated with CRC (genera Bacteroides, Clostridium, Filifactor, Fusobacterium, Gemella, Granulicatella, Parvimonas, Peptostreptococcus, Prevotella, Solobacterium, and Streptococcus). Clinical information, including patient demographics, comorbid medical conditions, date of bacteremia, and bacterial species identified, were collected. The incidence of biopsy-proved CRC was compared between the exposed and unexposed (patients without bacteremia matched for age, sex, and comorbidities) groups. The risk of CRC was increased in patients with bacteremia from B fragilis (hazard ratio [HR] = 3.85, 95% CI = 2.62-5.64, P = 5.5 × 10 In a retrospective analysis of patients hospitalized for bacteremia, we associated later diagnosis of CRC with B fragilis and S gallolyticus and other intestinal microbes. These bacteria might have entered the bloodstream from intestinal dysbiosis and perturbed barrier function. These findings support a model in which specific members of the intestinal microbiota promote colorectal carcinogenesis. Clinicians should evaluate patients with bacteremia from these species for neoplastic lesions in the colorectum.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2022
Publisher: American Society for Clinical Investigation
Date: 06-2007
DOI: 10.1172/JCI31561
Publisher: Springer Science and Business Media LLC
Date: 25-06-2022
DOI: 10.1038/S41467-022-31220-8
Abstract: The erse functions of WASP, the deficiency of which causes Wiskott-Aldrich syndrome (WAS), remain poorly defined. We generated three isogenic WAS models using patient induced pluripotent stem cells and genome editing. These models recapitulated WAS phenotypes and revealed that WASP deficiency causes an upregulation of numerous RNA splicing factors and widespread altered splicing. Loss of WASP binding to splicing factor gene promoters frequently leads to aberrant epigenetic activation. WASP interacts with dozens of nuclear speckle constituents and constrains SRSF2 mobility. Using an optogenetic system, we showed that WASP forms phase-separated condensates that encompasses SRSF2, nascent RNA and active Pol II. The role of WASP in gene body condensates is corroborated by ChIPseq and RIPseq. Together our data reveal that WASP is a nexus regulator of RNA splicing that controls the transcription of splicing factors epigenetically and the dynamics of the splicing machinery through liquid-liquid phase separation.
Location: United States of America
Location: United States of America
Location: Hong Kong
No related grants have been discovered for Christopher Benner.