Stories

PLK1 Inhibition Selectively Induces Apoptosis in ARID1A Deficient Cells Through Uncoupling of Oxygen Consumption from ATP Production. (Oncogene, Mar 22)

April 6, 2022

Inhibitors of the mitotic kinase PLK1 yield objective responses in a subset of refractory cancers. However, PLK1 overexpression in cancer does not correlate with drug sensitivity, and the clinical development of PLK1 inhibitors has been hampered by the lack of patient selection marker. Using a high-throughput chemical screen, we discovered that cells deficient for the tumor suppressor ARID1A are highly sensitive to PLK1 inhibition.

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Apr 06, 2022 CK Ong 0 comments
Clinical Translation of Patient-Derived Tumour Organoids- Bottlenecks and Strategies. (Biomark Res, Mar 22)

April 6, 2022

Multiple three-dimensional (3D) tumour organoid models assisted by multi-omics and Artificial Intelligence (AI) have contributed greatly to preclinical drug development and precision medicine. The intrinsic ability to maintain genetic and phenotypic heterogeneity of tumours allows for the reconciliation of shortcomings in traditional cancer models. While their utility in preclinical studies have been well established, little progress has been made in translational research and clinical trials. In this review, we identify the major bottlenecks preventing patient-derived tumour organoids (PDTOs) from being used in clinical setting.

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Apr 06, 2022 CK Ong 0 comments
ADARs act as potent regulators of circular transcriptome in cancer (Nat Commun, Mar 2022)

April 6, 2022

Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function.

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Apr 06, 2022 CK Ong 0 comments
CSI Singapore Researchers Discover Achilles Heel of High-Risk Multiple Myeloma (MM) Patients

April 6, 2022

Chromosomal abnormalities are found in most multiple myeloma (MM) patients. While myeloma patients have generally benefited from the advancement of treatment modalities over the years, the treatment outcome for patients having 2 or more high-risk prognostic events remains poor. In a novel step forward, researchers from Prof. Chng Wee Joo’s laboratory embarked on a study which aims to address the unmet clinical need in this group of patients.

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Apr 06, 2022 CK Ong 2 comments
MYC overexpression leads to increased chromatin interactions at superenhancers and MYC binding sites. (Genome Res, Feb 2022)

March 7, 2022

The MYC oncogene encodes for the MYC protein and is frequently dysregulated across multiple cancer cell types, making it an attractive target for cancer therapy. MYC overexpression leads to MYC binding at active enhancers, resulting in a global transcriptional amplification of active genes. Since superenhancers are frequently dysregulated in cancer, we hypothesized that MYC preferentially invades into superenhancers and alters the cancer genome organization.

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Mar 07, 2022 CK Ong 0 comments
p53-NEIL1 co-abnormalities induce genomic instability and promote synthetic lethality with Chk1 inhibition in multiple myeloma having concomitant 17p13(del) and 1q21(gain). (Oncogene, Feb 2022)

March 7, 2022

17p13(del) and 1q21(gain) are critical and independent high-risk cytogenetic markers, however, the biological significance underlying the poor outcome in MM patients having co-occurrence of both these chromosomal aberrations has never been interrogated. Herein, we identified that patients harbouring concomitant 17p13(del) with 1q21(gain) demonstrated the worst prognosis as compared to patients with single- (either 17p13(del) or 1q21(gain)) and with no chromosomal events (WT for both chromosomal loci); and they are highly enriched for genomic instability (GI) signature.

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Mar 07, 2022 CK Ong 0 comments
Global analysis of RNA-binding proteins identifies a positive feedback loop between LARP1 and MYC that promotes tumorigenesis. (Cell Mol Life Sci, Feb 2022)

March 7, 2022

In addition to genomic alterations, aberrant changes in post-transcriptional regulation can modify gene function and drive cancer development. RNA-binding proteins (RBPs) are a large class of post-transcriptional regulators that have been increasingly implicated in carcinogenesis. By integrating multi-omics data, we identify LARP1 as one of the most upregulated RBPs in colorectal cancer (CRC) and demonstrate its oncogenic properties.

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Mar 07, 2022 CK Ong 0 comments
Uncover the Mysterious, Culpable “Super-Enhancers” in Aggressive Blood Cancer

February 9, 2022

Multiple myeloma (MM) is the second most common blood cancer and remains an incurable disease. In a novel step forward, Prof. Chng Wee Joo’s group identified the mysterious and culpable “super-enhancers” in MM. By performing epigenomic enhancer profiling, findings established HJURP as an SE-associated gene of t(4;14)-positive multiple myeloma. This study highlights the potential of super enhancer profiling as an efficient platform to stamp out MM as well as other types of cancer.

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Feb 09, 2022 CK Ong 0 comments
ChIP-AP: An Integrated Analysis Pipeline for Unbiased ChIP-seq Analysis. (Brief Bioinform, Jan 2022)

February 3, 2022

Chromatin immunoprecipitation coupled with sequencing (ChIP-seq) is a technique used to identify protein-DNA interaction sites through antibody pull-down, sequencing and analysis; with enrichment 'peak' calling being the most critical analytical step. Benchmarking studies have consistently shown that peak callers have distinct selectivity and specificity characteristics that are not additive and seldom completely overlap in many scenarios, even after parameter optimization. We therefore developed ChIP-AP, an integrated ChIP-seq analysis pipeline utilizing four independent peak callers, which seamlessly processes raw sequencing files to final result.

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Feb 03, 2022 CK Ong 0 comments
A Point Mutation R122C in RUNX3 Promotes the Expansion of Isthmus Stem Cells and Inhibits Their Differentiation in the Stomach. (Cell Mol Gastroenterol Hepatol, Jan 2022)

February 3, 2022

RUNX3R122C missense mutation is associated with the continuous cycling of isthmus stem/progenitor cells, maturation arrest and development of a precancerous state. This work highlights the importance of RUNX3 in prevention of metaplasia and gastric cancer.

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Feb 03, 2022 CK Ong 0 comments
MiR-138 is a Potent Regulator of the Heterogenous MYC Transcript Population in Cancers. (Oncogene, Dec 2021)

February 3, 2022

In this study, we demonstrate that the MYC 3'UTR is shortened in colorectal cancer (CRC). Using unbiased computational and experimental approaches, we identify and validate microRNAs that target the MYC coding region. In particular, we show that miR-138 inhibits MYC expression and suppresses tumor growth of CRC and hepatocellular carcinoma (HCC) cell lines.

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Feb 03, 2022 CK Ong 0 comments
Immunohistochemistry Study of Tumor Vascular Normalization and Anti-Angiogenic Effects of Sunitinib Versus Bevacizumab Prior to Dose-Dense Doxorubicin/Cyclophosphamide Chemotherapy in HER2-Negative Breast Cancer. (Breast Cancer Res Treat, Dec 2021)

December 24, 2021

Tumor angiogenesis controlled predominantly by vascular endothelial growth factor and its receptor (VEGF-VEGFR) interaction plays a key role in the growth and propagation of cancer cells. However, the newly formed network of blood vessels is disorganized and leaky.

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Dec 24, 2021 CK Ong 0 comments
Super enhancer-mediated upregulation of HJURP promotes growth and survival of t(4;14)-positive multiple myeloma (Cancer Res, Dec 2021)

December 24, 2021

Multiple myeloma (MM) is an incurable malignancy with marked clinical and genetic heterogeneity. The cytogenetic abnormality t(4;14) (p16.3;q32.3) confers aggressive behavior in MM. Recently, essential oncogenic drivers in a wide range of cancers have been shown to be controlled by super-enhancers (SE).

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Dec 24, 2021 CK Ong 0 comments
Antisense RNAs Influence Promoter Usage of Their Counterpart Sense Genes in Cancer. (Cancer Res, Dec 2021)

December 24, 2021

Multiple noncoding natural antisense transcripts (ncNAT) are known to modulate key biological events such as cell growth or differentiation. However, the actual impact of ncNATs on cancer progression remains largely unknown. In this study, we identified a complete list of differentially expressed ncNATs in hepatocellular carcinoma.

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Dec 24, 2021 CK Ong 0 comments
CSI Congratulates the Recipients of the ASH Abstract Achievement Award!

November 30, 2021

Congratulations to Dr. Nurulhuda Binte Mustafa, a CSI Senior Research Fellow and Ms. Sinan Xiong, a CSI PhD student on receiving the ASH Abstract Achievement Award!

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Nov 30, 2021 C K Sangamitha 0 comments
13th Frontiers in Cancer Science (FCS) Conference Concluded Successfully

November 18, 2021

The 13th Frontiers in Cancer Science (FCS) conference, held over 3 days from 1 – 3 November 2021, concluded successfully with over 1,270 registrants from around the world. The nation’s largest annual conference was held virtually for the second year in a row, this time reaching out to a wider range of participants hailing from over 40 countries, including India, the United States, Malaysia, United Kingdom and more.

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Nov 18, 2021 CK Ong 0 comments
Pseudogene-Mediated DNA Demethylation Leads to Oncogene Activation. (Sci Adv, Oct 2021)

November 3, 2021

Pseudogenes, noncoding homologs of protein-coding genes, once considered nonfunctional evolutionary relics, have recently been linked to patient prognoses and cancer subtypes. Despite this potential clinical importance, only a handful of >12,000 pseudogenes in humans have been characterized in cancers to date.

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Nov 03, 2021 CK Ong 0 comments
Enhanced Penetrative siRNA Delivery by a Nanodiamond Drug Delivery Platform Against Hepatocellular Carcinoma 3D Models. (Nanoscale, Oct 2021)

November 3, 2021

Small interfering RNA (siRNA) can cause specific gene silencing and is considered promising for treating a variety of cancers, including hepatocellular carcinoma (HCC). However, siRNA has many undesirable physicochemical properties that limit its application. Additionally, conventional methods for delivering siRNA are limited in their ability to penetrate solid tumors.

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Nov 03, 2021 CK Ong 0 comments
Integrative Epigenomic and High-Throughput Functional Enhancer Profiling Reveals Determinants of Enhancer Heterogeneity in Gastric Cancer. (Genome Med, Oct 2021)

November 3, 2021

Our results indicate that combining histone modification and functional assay data may provide a more accurate metric to assess enhancer activity than either platform individually, providing insights into the relative contribution of genetic (cis) and regulatory (trans) mechanisms to GC enhancer functional heterogeneity.

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Nov 03, 2021 CK Ong 0 comments
CSI Researchers Unveil Novel Insights into the Induction of Gastric Carcinogenesis

October 28, 2021

Within the stomach corpus (main body), tubular invaginations are divided into regions known as the pit, isthmus, neck and base. In particular, the isthmus comprises rapidly proliferating cells, known as isthmus stem cells. Since the inner lining of the stomach is constantly damaged by food, pathogens and foreign substances, the isthmus plays an important role in replacing damaged tissue with new cells quickly apart from generating various mature cells in the corpus, such as acid-producing parietal cells, chief cells and mucin-producing mucous cells.

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Oct 28, 2021 CK Ong 0 comments