Yue Wan

Email Address
bchwany@nus.edu.sg


Organizational Units
OrgUnit Logo
Organizational Unit
OrgUnit Logo
Organizational Unit
BIOCHEMISTRY
dept

Filters

2019 - 201912020 - 20212
Reset filters

Settings

Citations

Publication Search Results

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Publication
    MiR-582-5p is a tumor suppressor microRNA targeting the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer
    (MDPI AG, 2021-02-11) Zhu, Bowen; Mitheera, V; Finch-Edmondson, Megan; Lee, Yaelim; Wan, Yue; Sudol, Marius; DasGupta, Ramanuj; PHYSIOLOGY; BIOCHEMISTRY
    The Hippo-YAP/TAZ signaling pathway is an evolutionarily conserved signaling pathway involved in a broad spectrum of biological processes, including tumorigenesis. Whilst aberrant Hippo-YAP/TAZ signaling is frequently reported in various cancers, the genetic alterations of this pathway are relatively rare, suggesting regulation at the post-transcriptional level. MicroRNAs play key role in tumorigenesis by regulating gene expression post-transcriptionally. Amongst the cancer-relevant microRNAs, miR-582-5p suppresses cell growth and tumorigenesis by inhibiting the expression of oncogenes, including AKT3, MAP3K2 and NOTCH1. Given the oncogenic role of YAP/TAZ in solid tumors, we scrutinized the possible interplay between miR- 582-5p and Hippo-YAP/TAZ signaling. Correlation analysis in NSCLC cells revealed a positive relationship between the expression of mature miR-582-5p and the proportion of phosphorylated YAP/TAZ. Intriguingly, YAP/TAZ knockdown reduced the expression of mature miR-582-5p but increased that of primary miR-582. Overexpression of miR-582-5p resulted in increased phosphorylation of YAP/TAZ with a concomitant reduction in cell proliferation and enhanced apoptosis. Mechanistically, we find that miR-582-5p targets actin regulators NCKAP1 and PIP5K1C, which may be responsible for the observed alteration in F-actin, known to modulate YAP/TAZ. We postulate that regulation of the actin cytoskeleton by miR-582-5p may attenuate YAP/TAZ activity. Altogether, this study reveals a novel mechanism of YAP/TAZ regulation by miR-582-5p in a cytoskeleton-dependent manner and suggests a negative feedback loop, highlighting the therapeutic potential of restoring miR-582-5p expression in treating NSCLC. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
  • No Thumbnail Available
    Publication
    Structure mapping of dengue and Zika viruses reveals functional long-range interactions
    (Nature Publishing Group, 2019) Huber, R.G.; Lim, X.N.; Ng, W.C.; Sim, A.Y.L.; Poh, H.X.; Shen, Y.; Lim, S.Y.; Sundstrom, K.B.; Sun, X.; Aw, J.G.; Too, H.K.; Boey, P.H.; Wilm, A.; Chawla, T.; Choy, M.M.; Jiang, L.; de Sessions, P.F.; Loh, X.J.; Alonso, S.; Hibberd, M.; Nagarajan, N.; Ooi, E.E.; Bond, P.J.; Sessions, O.M.; Wan, Y.; MICROBIOLOGY AND IMMUNOLOGY; MATERIALS SCIENCE AND ENGINEERING; DUKE-NUS MEDICAL SCHOOL; BIOCHEMISTRY
    Dengue (DENV) and Zika (ZIKV) viruses are clinically important members of the Flaviviridae family with an 11 kb positive strand RNA genome that folds to enable virus function. Here, we perform structure and interaction mapping on four DENV and ZIKV strains inside virions and in infected cells. Comparative analysis of SHAPE reactivities across serotypes nominates potentially functional regions that are highly structured, conserved, and contain low synonymous mutation rates. Interaction mapping by SPLASH identifies many pair-wise interactions, 40% of which form alternative structures, suggesting extensive structural heterogeneity. Analysis of shared interactions between serotypes reveals a conserved macro-organization whereby interactions can be preserved at physical locations beyond sequence identities. We further observe that longer-range interactions are preferentially disrupted inside cells, and show the importance of new interactions in virus fitness. These findings deepen our understanding of Flavivirus genome organization and serve as a resource for designing therapeutics in targeting RNA viruses. © 2019, The Author(s).
  • No Thumbnail Available
    Publication
    Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions
    (Nature Research, 2021-08-25) Yang, Siwy Ling; Defalco, Louis; Anderson, Danielle E.; Zhang, Yu; Aw, Jong Ghut Ashley; Lim, Su Ying; Lim, Xin Ni; Tan, Kiat Yee; Zhang, Tong; Chawla, Tanu; Su, Yan; Lezhava, Alexander; Merits, Andres; Wang, Lin-Fa; Huber, Roland G.; Wan, Yue; DUKE-NUS MEDICAL SCHOOL; BIOCHEMISTRY
    SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (?382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, observe that subgenomic RNAs can form different structures, and that WT and ?382 virus genomes fold differently. Proximity ligation sequencing identify hundreds of RNA-RNA interactions within the virus genome and between the virus and host RNAs. SARS-CoV-2 genome binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2’-O-methylated. 2’-O-methylation sites are enriched in viral untranslated regions, associated with increased virus pair-wise interactions, and are decreased in host mRNAs upon virus infection, suggesting that the virus sequesters methylation machinery from host RNAs towards its genome. These studies deepen our understanding of the molecular and cellular basis of SARS-CoV-2 pathogenicity and provide a platform for targeted therapy. © 2021, The Author(s).