Shing Hooi - Academia.edu (original) (raw)

Papers by Shing Hooi

Experimental and Molecular Medicine, Nov 16, 2022

The hypothalamus has been shown to be densely populated by galanin-containing neuron cell bodies.... more The hypothalamus has been shown to be densely populated by galanin-containing neuron cell bodies. The greatest concentration of cells reside in the arcuate nucleus. In addition, galanin immunopositive cells are present in the paraventricular (PVN), supraoptic (SON) and dorsomedial nuclei (Rokaeus et al., 1984; Ch’ng et al., 1985; Skofitsch et al., 1985; Melander et al., 1985, 1986; Palkovits et al., 1987). Galanin-containing nerve fibers are found throughout the hypothalamus but the median eminence (ME) contains the highest concentration of galanin in the brain (Skofitsch et al., 1986; Gabriel et al., 1988). Autoradiographic binding studies also demonstrated that galanin receptors are concentrated in the ME (Melander et al., 1986; Skofitsch et al., 1987). Much of the galanin in the ME originates in the arcuate nucleus (Gabriel et al., 1988) but the PVN and SON also contribute substantial amounts of galanin to the ME (Palkovits et al., 1987). Furthermore, Levin et al. (1987) and Holets et al. (1988) demonstrated that brainstem neurons containing galanin project to both the PVN and SON. These inputs probably relay hemodynamic information to these nuclei.

Cancer Research, Apr 15, 2006

Epithelial-mesenchymal transition (EMT) in cancer cells plays a pivotal role in determining metas... more Epithelial-mesenchymal transition (EMT) in cancer cells plays a pivotal role in determining metastatic prowess, but knowledge of EMT regulation remains incomplete. In this study, we defined a critical functional role for the Forkhead transcription factor FOXQ1 in regulating EMT in breast cancer cells. FOXQ1 expression was correlated with high-grade basal-like breast cancers and was associated with poor clinical outcomes. RNAi-mediated suppression of FOXQ1 expression in highly invasive human breast cancer cells reversed EMT, reduced invasive ability, and alleviated other aggressive cancer phenotypes manifested in 3-dimensional Matrigel (BD Biosciences) culture. Conversely, enforced expression of FOXQ1 in differentiated human mammary epithelial cells (HMLER) or epithelial cancer cell lines provoked an epithelial to mesenchymal morphologic change, gain of stem cell–like properties, and acquisition of resistance to chemotherapy-induced apoptosis. Mechanistic investigations revealed that FOXQ1-induced EMT was associated with transcriptional inactivation of the epithelial regulator E-cadherin (CDH1). Our findings define a key role for FOXQ1 in regulating EMT and aggressiveness in human cancer. Cancer Res; 71(8); 3076–86. ©2011 AACR.

Supplementary Table 3 from FOXQ1 Regulates Epithelial-Mesenchymal Transition in Human Cancers

Supplementary Table 2 from FOXQ1 Regulates Epithelial-Mesenchymal Transition in Human Cancers

InTech eBooks, Apr 5, 2017

Acta pharmacologica Sinica, Jun 15, 2020

Proceedings of the American Association for Cancer Research Annual Meeting, Aug 20, 2003

Cell Death and Disease, Dec 13, 2012

Korean Journal of Medical Education, 2018

European Journal of Cancer Supplements, 2006

Galanin, 1991

Over the past several decades, we have come to appreciate the central role of intercellular commu... more Over the past several decades, we have come to appreciate the central role of intercellular communication in the regulation of normal homeostasis. Effective communication requires a dynamic web of pathways that carry precise, and informative, messages. Several classes of molecules have been shown to carry these messages, including nucleosides, amino acids, complex amines, carbohydrates, steroids, and peptides. Our understanding of the importance of small peptides in this communications network has been expanded by the physiological and pharmacological studies of numerous investigators over the past sixty years. This understanding has led to a search for additional peptide mediators to account for the exquisite subtleties of intercellular communication. Dr. Victor Mutt, whom we honor by this volume, has led the efforts to identify and characterize such peptides and is responsible for the discovery of several of the most important of them. As described elsewhere in this volume, one of the more recent products of these investigations is galanin, an amidated peptide isolated and purified from copious quantities of porcine intestinal extracts (Tatemoto et al., 1983). Amino acid sequence and structural analysis suggest that galanin is unrelated to any of the other known families of regulatory peptides, and to date it remains the only known member of its own family.

Cancers, 2020

Cytoskeletal proteins, which consist of different sub-families of proteins including microtubules... more Cytoskeletal proteins, which consist of different sub-families of proteins including microtubules, actin and intermediate filaments, are essential for survival and cellular processes in both normal as well as cancer cells. However, in cancer cells, these mechanisms can be altered to promote tumour development and progression, whereby the functions of cytoskeletal proteins are co-opted to facilitate increased migrative and invasive capabilities, proliferation, as well as resistance to cellular and environmental stresses. Herein, we discuss the cytoskeletal responses to important intracellular stresses (such as mitochondrial, endoplasmic reticulum and oxidative stresses), and delineate the consequences of these responses, including effects on oncogenic signalling. In addition, we elaborate how the cytoskeleton and its associated molecules present themselves as therapeutic targets. The potential and limitations of targeting new classes of cytoskeletal proteins are also explored, in the...

Medical Teacher, 2020

The process for introducing and developing a program for teaching medical professionalism at the ... more The process for introducing and developing a program for teaching medical professionalism at the National University of Singapore, School of Medicine is outlined. Professionalism was recognised as embracing 'honesty and integrity,' 'responsibility and participation,' 'respect and sensitivity,' and 'compassion and empathy.' Those broad values are expressed as specific attitudes and behaviours that are taught and assessed throughout the course. Honesty and integrity, for example, are demonstrated by 'presenting original, authentic assignments' (in medical education); and 'accepting personal mistakes and honestly acknowledging them' (in clinical training and practice). Values and items of behaviour were drawn from the literature, and reviewed and refined to address needs identified within the Medical School. A broad spectrum of pre-clinical and clinical teachers contributed to this development. The program was reassessed to determine the extent to which it has been implemented and has evolved following its adoption. The results are confirming in that: the majority of recommendations have been implemented; the program has developed further; and is supported by ancillary student enrichment activities. Medical professionalism has been given prominence through all phases of the course. Nevertheless, challenges remain and particularly in the extent to which medical professionalism is taught and assessed in various clinical postings.

Biochemical and Biophysical Research Communications, 2019

Background: CCAAT enhancer binding protein a (C/EBPa), as an important transcription factor invol... more Background: CCAAT enhancer binding protein a (C/EBPa), as an important transcription factor involved in cell proliferation, differentiation and metabolism, was up-regulated in primary hepatocellular carcinoma (HCC) and predicted poorer prognosis. In this study, we explored how histone deacetylases (HDACs) up-regulated C/EBPa in HCC. Methods: The protein expressions of HDAC1, HDAC2 were associated with C/EBPa by immunohistochemistry staining in a HCC tissue microarray. HCC cells were then treated with HDAC inhibitors or siRNAs to determine the roles of miR-124-3p and miR-25 in the regulation of C/EBPa mRNA expression. Results: Both HDAC1 and HDAC2 proteins were significantly associated with C/EBPa. Inhibition of HDAC by either pharmacological inhibitors or siRNAs decreased C/EBPa mRNA expression in dose-dependent manners in HCC cells. HDAC inhibitors reduced C/EBPa mRNA stability as shown by pmiRGLO luciferase reporter assays. HDAC inhibition consistently induced miR-124-3p and miR-25 expression. Conversely, blockage of miR-124-3p and/or miR-25 by treatment with specific synthetic inhibitors abolished C/EBPa reduction. More importantly, C/EBPa mRNA stability could be rescued by site-directed mutations of miR-124-3p or miR-25 recognition sites in the C/EBPa 3 0 UTR sequence. In summary, HDAC may up-regulate C/EBPa expression through miR-124-3p and miR-25 in HCC.

Cytotechnology, 2019

The tumor suppressor DLEC1 has been shown to promote cell proliferation when AP-2a2 is down-regul... more The tumor suppressor DLEC1 has been shown to promote cell proliferation when AP-2a2 is down-regulated in HCT116 stable clones, suggesting its pro-survival nature. However, the pro-survival function of DLEC1 has not been confirmed in other cells and its underlying mechanisms remain elusive. Therefore, we knocked down DLEC1 in a panel of cell lines and found that DLEC1 depletion caused various extents of cell death through intrinsic pathway. DLEC1 overexpression promoted cell survival and reduced cell death in cancer cells after 5-FU treatment, while DLEC1 down-regulation sensitized cancer cells to 5-FU. Further studies demonstrated that DLEC1 attenuated the increase in cleaved PARP, caspase-3 and caspase-7, the activity of caspase-9 and the diffusion of cytosolic cytochrome c from mitochondria. Our data also showed that BCL-XL was up-regulated by DLEC1 in stable clones after 5-FU treatment. Altogether, these results indicated that DLEC1 protects cells against cell death induced by 5-FU through the attenuation of active proteins in caspase cascade and the up-regulation of BCL-XL. Therefore, DLEC1 can be a pro-survival protein under certain circumstances and a potential therapeutic target for increasing sensitivity of cancer cells to 5-FU.

International Journal of Oncology, 2000

Ribosomal protein L7a (rp L7a) was identified in a subtractive hybridization screen as a gene up-... more Ribosomal protein L7a (rp L7a) was identified in a subtractive hybridization screen as a gene up-regulated in human colorectal cancer. Expression of rp L7a was greater than 2-fold higher in tumors compared to adjacent normal mucosa in 72% of the patients studied (n=36). rp L7a was also up-regulated in concomitant polyps. The number of patients with rp L7a T/N ratio of >2 was significantly higher in the female (16/18) than in the male (10/18). rp L7a expression was also significantly higher in females with lymph node involvement compared to males. These results indicate that rp L7a expression is related to tumor growth in colorectal cancer especially in females, where it may also be related to tumor spread. There was no correlation of rp L7a expression with tumor cell differentiation. We also show that rp L7a does not exist as a fusion oncogene (trk-2h) in colorectal cancer.