Displaying publications 1 - 20 of 59 in total

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  1. Fulltext Molecular characterization of serous ovarian carcinoma using a multigene next generation sequencing cancer panel approach
    Ab Mutalib NS, Syafruddin SE, Md Zain RR, Mohd Dali AZ, Mohd Yunos RI, Saidin S, et al.
    BMC Res Notes, 2014;7:805.
    PMID: 25404506 DOI: 10.1186/1756-0500-7-805
    High grade serous ovarian cancer is one of the poorly characterized malignancies. This study aimed to elucidate the mutational events in Malaysian patients with high grade serous ovarian cancer by performing targeted sequencing on 50 cancer hotspot genes.
  2. Fulltext Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis
    Ab Mutalib NS, Othman SN, Mohamad Yusof A, Abdullah Suhaimi SN, Muhammad R, Jamal R
    PeerJ, 2016;4:e2119.
    PMID: 27350898 DOI: 10.7717/peerj.2119
    Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process. Objectives. We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC. Results. PTC patients with LNM (PTC LNM-P) have a significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found four significant enrichment pathways potentially involved in metastasis to the lymph nodes, namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine-cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p = 4.70E-06) involving downregulation of 90 OxPhos-related genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB transcription factors were identified exclusively in PTC LNM-P versus PTC LNN. Conclusion. We found evidence of five miRNAs differentially expressed in PTC LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to the lymph node in PTC. We postulate that hsa-miR-301b might be involved in regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of our knowledge, the roles of these TFs have been studied in PTC but the precise role of this miRNA with these TFs in LNM in PTC has not been investigated.
  3. Fulltext Pharmacogenomics DNA Biomarkers in Colorectal Cancer: Current Update
    Ab Mutalib NS, Md Yusof NF, Abdul SN, Jamal R
    Front Pharmacol, 2017;8:736.
    PMID: 29075194 DOI: 10.3389/fphar.2017.00736
    Colorectal cancer (CRC) remains as one of the most common cause of worldwide cancer morbidity and mortality. Improvements in surgical modalities and adjuvant chemotherapy have increased the cure rates in early stage disease, but a significant portion of the patients will develop recurrence or advanced disease. The efficacy of chemotherapy of recurrence and advanced CRC has improved significantly over the last decade. Previously, the historical drug 5-fluorouracil was used as single chemotherapeutic agent. Now with the addition of other drugs such as capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, vemurafenib, and dabrafenib, the median survival of patients with advanced CRC has significantly improved from less than a year to the current standard of almost 2 years. However, the side effects of systemic therapy such as toxicity may cause fatal complications and have a major consequences on the patients' quality of life. Hence, there is an urgent need for key biomarkers which will enable the selection of optimal drug singly or in combination for an individual patient. The application of personalized therapy based on DNA testing could aid the clinicians in providing the most effective chemotherapy agents and dose modifications for each patient. Yet, some of the current findings are controversial and the evidences are conflicting. This review aims at summarizing the current state of knowledge about germline pharmacogenomics DNA variants that are currently used to guide therapeutic decisions and variants that have the potential to be clinically useful in the future. In addition, current updates on germline variants conferring treatment sensitivity, drug resistance to existing chemotherapy agents and variants affecting prognosis and survival will also be emphasized. Different alteration in the same gene might confer resistance or enhanced sensitivity; and while most of other published reviews generally stated only the gene name and codon location, we will specifically discuss the exact variants to offer more accurate information in this mini review.
  4. Fulltext Impact of Chemotherapy on Extracellular Vesicles: Understanding the Chemo-EVs
    Ab Razak NS, Ab Mutalib NS, Mohtar MA, Abu N
    Front Oncol, 2019;9:1113.
    PMID: 31803605 DOI: 10.3389/fonc.2019.01113
    Chemotherapy is the standard go-to treatment for cancer besides surgery and radiation. It has recently come to light that the interaction between chemotherapy and the immune system is important in maintaining tumor immunity as well as influencing the efficacy of the therapy. However, ample preclinical studies have shown that in addition to direct cytotoxic effects on cancer cells, a fraction of chemotherapeutic agents may promote immunogenic cell death, and alter the inflammatory milieu of the tumor microenvironment. Extracellular vesicles (EV) have been shown to interact with the tumor microenvironment by delivering alterative signals to the surrounding cells; as a result, this results in interference with each cell's capability to eradicate tumors or gives advantages to cancer cells so as to survive therapy. Chemotherapy-induced extracellular vesicles (chemo-EVs) have been theorized to be carrying different cargo loads than non-chemotherapy-induced EVs. Aside from chemoresistance, there is growing evidence to suggest that chemo-EVs could dictate tumor behavior, especially in terms of metastasis, immune response, and cancer stemness. This mini-review attempts to summarize and evaluate recent developments on the role of chemo-EVs in other aspects of tumor-related processes.
  5. Fulltext Molecular Characterization of Somatic Alterations in Dukes' B and C Colorectal Cancers by Targeted Sequencing
    Abdul SN, Ab Mutalib NS, Sean KS, Syafruddin SE, Ishak M, Sagap I, et al.
    Front Pharmacol, 2017;8:465.
    PMID: 28769798 DOI: 10.3389/fphar.2017.00465
    Despite global progress in research, improved screening and refined treatment strategies, colorectal cancer (CRC) remains as the third most common malignancy. As each type of cancer is different and exhibits unique alteration patterns, identifying and characterizing gene alterations in CRC that may serve as biomarkers might help to improve diagnosis, prognosis and predict potential response to therapy. With the emergence of next generation sequencing technologies (NGS), it is now possible to extensively and rapidly identify the gene profile of individual tumors. In this study, we aimed to identify actionable somatic alterations in Dukes' B and C in CRC via NGS. Targeted sequencing of 409 cancer-related genes using the Ion Ampliseq(TM) Comprehensive Cancer Panel was performed on genomic DNA obtained from paired fresh frozen tissues, cancer and normal, of Dukes' B (n = 10) and Dukes' C (n = 9) CRC. The sequencing results were analyzed using Torrent Suite, annotated using ANNOVAR and validated using Sanger sequencing. A total of 141 somatic non-synonymous sequence variations were identified in 86 genes. Among these, 64 variants (45%) were predicted to be deleterious, 38 variants (27%) possibly deleterious while the other 39 variants (28%) have low or neutral protein impact. Seventeen genes have alterations with frequencies of ≥10% in the patient cohort and with 14 overlapped genes in both Dukes' B and C. The adenomatous polyposis coli gene (APC) was the most frequently altered gene in both groups (n = 6 in Dukes' B and C). In addition, TP53 was more frequently altered in Dukes' C (n = 7) compared to Dukes' B (n = 4). Ten variants in APC, namely p.R283(∗), p.N778fs, p.R805(∗), p.Y935fs, p.E941fs, p.E1057(∗), p.I1401fs, p.Q1378(∗), p.E1379(∗), and p.A1485fs were predicted to be driver variants. APC remains as the most frequently altered gene in the intermediate stages of CRC. Wnt signaling pathway is the major affected pathway followed by P53, RAS, TGF-β, and PI3K signaling. We reported the alteration profiles in each of the patient which has the potential to affect the clinical decision. We believe that this study will add further to the understanding of CRC molecular landscape.
  6. Identification of differentially expressed circular RNAs in chemoresistant colorectal cancer
    Abu N, Hon KW, Jeyaraman S, Yahaya A, Abdullah NM, Mustangin M, et al.
    Epigenomics, 2019 06;11(8):875-884.
    PMID: 31020847 DOI: 10.2217/epi-2019-0042
    Aim: Chemoresistance in colorectal cancer (CRC) has become a burden in treating the disease effectively. Circular RNAs (circRNAs) are a type of noncoding RNA that were found to be important in cellular homeostasis. The involvement of circRNAs in relation to chemoresistance in other types of cancers has also been reported. This study aims to identify the differentially expressed circRNAs between chemoresistant and chemosensitive CRC cells. Materials & methods: We developed a chemoresistant cell line model and profiled the circRNAs via microarray. We further validated the expression of two circRNAs in 25 formalin-fixed paraffin-embedded (FFPE) tissue specimens (13 nonresponders and 12 responders) via quantitative polymerase chain reaction (qPCR).  Results & conclusion: We found that there were 773 upregulated and 732 downregulated circRNAs between the chemoresistant and chemosensitive HCT-116 cells. We found that hsa_circ_32883 could be a promising biotarget.
  7. Fulltext Methylation Profile of Cancer Testis Antigens in Colorectal Cancer
    Abu N, Rus Bakarurraini NAA, Nasir SN, Ishak M, Baharuddin R, Jamal R, et al.
    Iran J Immunol, 2023 Mar 14;20(1):83-91.
    PMID: 36932973 DOI: 10.22034/iji.2023.92600.2171
    BACKGROUND: Cancer testis antigens (CTAs) are a class of immune-stimulating antigens often overexpressed in many types of cancers. The usage of the CTAs as immunotherapy targets have been widely investigated in different cancers including melanoma, hematological malignancies, and colorectal cancer. Studies have indicated that the epigenetic regulation of the CTAs such as the methylation status may affect the expression of the CTAs. However, the report on the methylation status of the CTAs is conflicting. The general methylation profile of the CTAs, especially in colorectal cancer, is still elusive.

    OBJECTIVE: To determine the methylation profile of the selected CTAs in our colorectal cancer patients.

    METHODS: A total of 54 pairs of colorectal cancer samples were subjected to DNA methylation profiling using the Infinium Human Methylation 450K bead chip.

    RESULTS: We found that most of the CTAs were hypomethylated, and CCNA1 and TMEM108 genes were among the few CTAs that were hypermethylated.

    CONCLUSION: Overall, our brief report has managed to show the overall methylation profile in over the 200 CTAs in colorectal cancer and this could be used for further refining any immunotherapy targets.

  8. Fulltext Global metabolomics profiling of colorectal cancer in Malaysian patients
    Amir Hashim NA, Ab-Rahim S, Wan Ngah WZ, Nathan S, Ab Mutalib NS, Sagap I, et al.
    Bioimpacts, 2021;11(1):33-43.
    PMID: 33469506 DOI: 10.34172/bi.2021.05
    Introduction:
    The serum metabolomics approach has been used to identify metabolite biomarkers that can diagnose colorectal cancer (CRC) accurately and specifically. However, the biomarkers identified differ between studies suggesting that more studies need to be performed to understand the influence of genetic and environmental factors. Therefore, this study aimed to identify biomarkers and affected metabolic pathways in Malaysian CRC patients.
    Methods:
    Serum from 50 healthy controls and 50 CRC patients were collected at UKM Medical Centre. The samples were deproteinized with acetonitrile and untargeted metabolomics profile determined using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOFMS, Agilent USA). The data were analysed using Mass Profiler Professional (Agilent, USA) software. The panel of biomarkers determined were then used to identify CRC from a new set of 20 matched samples.
    Results:
    Eleven differential metabolites were identified whose levels were significantly different between CRC patients compared to normal controls. Based on the analysis of the area under the curve, 7 of these metabolites showed high sensitivity and specificity as biomarkers. The use of the 11 metabolites on a new set of samples was able to differentiate CRC from normal samples with 80% accuracy. These metabolites were hypoxanthine, acetylcarnitine, xanthine, uric acid, tyrosine, methionine, lysoPC, lysoPE, citric acid, 5-oxoproline, and pipercolic acid. The data also showed that the most perturbed pathways in CRC were purine, catecholamine, and amino acid metabolisms.
    Conclusion:
    Serum metabolomics profiling can be used to identify distinguishing biomarkers for CRC as well as to further our knowledge of its pathophysiological mechanisms.
  9. Fulltext A Keystone Gut Bacterium Christensenella minuta-A Potential Biotherapeutic Agent for Obesity and Associated Metabolic Diseases
    Ang WS, Law JW, Letchumanan V, Hong KW, Wong SH, Ab Mutalib NS, et al.
    Foods, 2023 Jun 26;12(13).
    PMID: 37444223 DOI: 10.3390/foods12132485
    A new next-generation probiotic, Christensenella minuta was first discovered in 2012 from healthy human stool and described under the phylum Firmicutes. C. minuta is a subdominant commensal bacterium with highly heritable properties that exhibits mutual interactions with other heritable microbiomes, and its relative abundance is positively correlated with the lean host phenotype associated with a low BMI index. It has been the subject of numerous studies, owing to its potential health benefits. This article reviews the evidence from various studies of C. minuta interventions using animal models for managing metabolic diseases, such as obesity, inflammatory bowel disease, and type 2 diabetes, characterized by gut microbiota dysbiosis and disruption of host metabolism. Notably, more studies have presented the complex interaction between C. minuta and host metabolism when it comes to metabolic health. Therefore, C. minuta could be a potential candidate for innovative microbiome-based biotherapy via fecal microbiota transplantation or oral administration. However, the detailed underlying mechanism of action requires further investigation.
  10. Fulltext SARS-CoV-2 genomic surveillance in Malaysia: displacement of B.1.617.2 with AY lineages as the dominant Delta variants and the introduction of Omicron during the fourth epidemic wave
    Azami NAM, Perera D, Thayan R, AbuBakar S, Sam IC, Salleh MZ, et al.
    Int J Infect Dis, 2022 Dec;125:216-226.
    PMID: 36336246 DOI: 10.1016/j.ijid.2022.10.044
    OBJECTIVES: This study reported SARS-CoV-2 whole genome sequencing results from June 2021 to January 2022 from seven genome sequencing centers in Malaysia as part of the national surveillance program.

    METHODS: COVID-19 samples that tested positive by reverse transcription polymerase chain reaction and with cycle threshold values <30 were obtained throughout Malaysia. Sequencing of SARS-CoV-2 complete genomes was performed using Illumina, Oxford Nanopore, or Ion Torrent platforms. A total of 6163 SARS-CoV-2 complete genome sequences were generated over the surveillance period. All sequences were submitted to the Global Initiative on Sharing All Influenza Data database.

    RESULTS: From June 2021 to January 2022, Malaysia experienced the fourth wave of COVID-19 dominated by the Delta variant of concern, including the original B.1.617.2 lineage and descendant AY lineages. The B.1.617.2 lineage was identified as the early dominant circulating strain throughout the country but over time, was displaced by AY.59 and AY.79 lineages in Peninsular (west) Malaysia, and the AY.23 lineage in east Malaysia. In December 2021, pilgrims returning from Saudi Arabia facilitated the introduction and spread of the BA.1 lineage (Omicron variant of concern) in the country.

    CONCLUSION: The changing trends of circulating SARS-CoV-2 lineages were identified, with differences observed between west and east Malaysia. This initiative highlighted the importance of leveraging research expertise in the country to facilitate pandemic response and preparedness.

  11. Gene Mutations as Emerging Biomarkers and Therapeutic Targets for Relapsed Acute Myeloid Leukemia
    Aziz H, Ping CY, Alias H, Ab Mutalib NS, Jamal R
    Front Pharmacol, 2017;8:897.
    PMID: 29270125 DOI: 10.3389/fphar.2017.00897
    It is believed that there are key differences in the genomic profile between adult and childhood acute myeloid leukemia (AML). Relapse is the significant contributor of mortality in patients with AML and remains as the leading cause of cancer death among children, posing great challenges in the treatment of AML. The knowledge about the genomic lesions in childhood AML is still premature as most genomic events defined in children were derived from adult cohorts. However, the emerging technologies of next generation sequencing have narrowed the gap of knowledge in the biology of AML by the detection of gene mutations for each sub-type which have led to the improvement in terms of prognostication as well as the use of targeted therapies. In this review, we describe the recent understanding of the genomic landscape including the prevalence of mutation, prognostic impact, and targeted therapies that will provide an insight into the pathogenesis of AML relapse in both adult and childhood cases.
  12. Fulltext Identification of Predictive DNA Methylation Biomarkers for Chemotherapy Response in Colorectal Cancer
    Baharudin R, Ab Mutalib NS, Othman SN, Sagap I, Rose IM, Mohd Mokhtar N, et al.
    Front Pharmacol, 2017;8:47.
    PMID: 28243201 DOI: 10.3389/fphar.2017.00047
    Resistance to 5-Fluorouracil (5-FU) is a major obstacle to the successful treatment of colorectal cancer (CRC) and posed an increased risk of recurrence. DNA methylation has been suggested as one of the underlying mechanisms for recurrent disease and its contribution to the development of drug resistance remains to be clarified. This study aimed to determine the methylation phenotype in CRC for identification of predictive markers for chemotherapy response. We performed DNA methylation profiling on 43 non-recurrent and five recurrent CRC patients using the Illumina Infinium HumanMethylation450 Beadchip assay. In addition, CRC cells with different genetic backgrounds, response to 5-FU and global methylation levels (HT29 and SW48) were treated with 5-FU and DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC). The singular and combined effects of these two drug classes on cell viability and global methylation profiles were investigated. Our genome-wide methylation study on the clinical specimens showed that recurrent CRCs exhibited higher methylation levels compared to non-recurrent CRCs. We identified 4787 significantly differentially methylated genes (P < 0.05); 3112 genes were hyper- while 1675 genes were hypomethylated in the recurrent group compared to the non-recurrent. Fifty eight and 47 of the significantly hypermethylated and hypomethylated genes have an absolute recurrent/non-recurrent methylation difference of ≥20%. Most of the hypermethylated genes were involved in the MAPK signaling pathway which is a key regulator for apoptosis while the hypomethylated genes were involved in the PI3K-AKT signaling pathway and proliferation process. We also demonstrate that 5-azadC treatment enhanced response to 5-FU which resulted in significant growth inhibition compared to 5-FU alone in hypermethylated cell lines SW48. In conclusion, we found the evidence of five potentially biologically important genes in recurrent CRCs that could possibly serve as a new potential therapeutic targets for patients with chemoresistance. We postulate that aberrant methylation of CCNEI, CCNDBP1, PON3, DDX43, and CHL1 in CRC might be associated with the recurrence of CRC and 5-azadC-mediated restoration of 5-FU sensitivity is mediated at least in part by MAPK signaling pathway.
  13. Fulltext Epigenetics of SFRP1: The Dual Roles in Human Cancers
    Baharudin R, Tieng FYF, Lee LH, Ab Mutalib NS
    Cancers (Basel), 2020 Feb 14;12(2).
    PMID: 32074995 DOI: 10.3390/cancers12020445
    Secreted frizzled-related protein 1 (SFRP1) is a gene that belongs to the secreted glycoprotein SFRP family. SFRP1 has been classified as a tumor suppressor gene due to the loss of expression in various human cancers, which is mainly attributed by epigenetic inactivation via DNA methylation or transcriptional silencing by microRNAs. Epigenetic silencing of SFRP1 may cause dysregulation of cell proliferation, migration, and invasion, which lead to cancer cells formation, disease progression, poor prognosis, and treatment resistance. Hence, restoration of SFRP1 expression via demethylating drugs or over-expression experiments opens the possibility for new cancer therapy approach. While the role of SFRP1 as a tumor suppressor gene is well-established, some studies also reported the possible oncogenic properties of SFRP1 in cancers. In this review, we discussed in great detail the dual roles of SFRP1 in cancers-as tumor suppressor and tumor promoter. The epigenetic regulation of SFRP1 expression will also be underscored with additional emphasis on the potentials of SFRP1 in modulating responses toward chemotherapeutic and epigenetic-modifying drugs, which may encourage the development of novel drugs for cancer treatment. We also present findings from clinical trials and patents involving SFRP1 to illustrate its clinical utility, extensiveness of each research area, and progression toward commercialization. Lastly, this review provides directions for future research to advance SFRP1 as a promising cancer biomarker.
  14. Fulltext Targeting Gut Microbial Biofilms-A Key to Hinder Colon Carcinogenesis?
    Chew SS, Tan LT, Law JW, Pusparajah P, Goh BH, Ab Mutalib NS, et al.
    Cancers (Basel), 2020 Aug 13;12(8).
    PMID: 32823729 DOI: 10.3390/cancers12082272
    Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
  15. Fulltext Vibrio vulnificus: An Environmental and Clinical Burden
    Heng SP, Letchumanan V, Deng CY, Ab Mutalib NS, Khan TM, Chuah LH, et al.
    Front Microbiol, 2017;8:997.
    PMID: 28620366 DOI: 10.3389/fmicb.2017.00997
    Vibrio vulnificus is a Gram negative, rod shaped bacterium that belongs to the family Vibrionaceae. It is a deadly, opportunistic human pathogen which is responsible for the majority of seafood-associated deaths worldwide. V. vulnificus infection can be fatal as it may cause severe wound infections potentially requiring amputation or lead to sepsis in susceptible individuals. Treatment is increasingly challenging as V. vulnificus has begun to develop resistance against certain antibiotics due to their indiscriminate use. This article aims to provide insight into the antibiotic resistance of V. vulnificus in different parts of the world as well as an overall review of its clinical manifestations, treatment, and prevention. Understanding the organism's antibiotic resistance profile is vital in order to select appropriate treatment and initiate appropriate prevention measures to treat and control V. vulnificus infections, which should eventually help lower the mortality rate associated with this pathogen worldwide.
  16. Fulltext miRNAs and lncRNAs as Predictive Biomarkers of Response to FOLFOX Therapy in Colorectal Cancer
    Hon KW, Abu N, Ab Mutalib NS, Jamal R
    Front Pharmacol, 2018;9:846.
    PMID: 30127741 DOI: 10.3389/fphar.2018.00846
    Chemotherapy is one of the options for cancer treatment. FOLFOX is one of the widely used chemotherapeutic regimens used to treat primarily colorectal cancer and other cancers as well. However, the emergence of chemo-resistance clones during cancer treatment has become a critical challenge in the clinical setting. It is crucial to identify the potential biomarkers and therapeutics targets which could lead to an improvement in the success rate of the proposed therapies. Since non-coding RNAs have been known to be important players in the cellular system, the interest in their functional roles has intensified. Non-coding RNAs (ncRNAs) as regulators at the post-transcriptional level could be very promising to provide insights in overcoming chemo-resistance to FOLFOX. Hence, this mini review attempts to summarize the potential of ncRNAs correlating with chemo-sensitivity/resistance to FOLFOX.
  17. Fulltext Exosomes As Potential Biomarkers and Targeted Therapy in Colorectal Cancer: A Mini-Review
    Hon KW, Abu N, Ab Mutalib NS, Jamal R
    Front Pharmacol, 2017;8:583.
    PMID: 28894420 DOI: 10.3389/fphar.2017.00583
    The number of colorectal cancer (CRC) cases have increased gradually year by year. In fact, CRC is one of the most widely diagnosed cancer in men and women today. This disease is usually diagnosed at a later stage of the development, and by then, the chance of survival has declined significantly. Even though substantial progress has been made in understanding the basic molecular mechanism of CRC, there is still a lack of understanding in using the available information for diagnosing CRC effectively. Liquid biopsies are minimally invasive and have become the epitome of a good screening source for stage-specific diagnosis, measuring drug response and severity of the disease. There are various circulating entities that can be found in biological fluids, and among them, exosomes, have been gaining considerable attention. Exosomes can be found in almost all biological fluids including serum, urine, saliva, and breast milk. Furthermore, exosomes carry valuable molecular information such as proteins and nucleic acids that directly reflects the source of the cells. Nevertheless, the inconsistent yield and isolation process and the difficulty in obtaining pure exosomes have become major obstacles that need to be addressed. The potential usage of exosomes as biomarkers have not been fully validated and explored yet. This review attempts to uncover the potential molecules that can be derived from CRC-exosomes as promising biomarkers or molecular targets for effective diagnosing of CRC.
  18. Fulltext Extracellular Vesicle-derived circular RNAs confers chemoresistance in Colorectal cancer
    Hon KW, Ab-Mutalib NS, Abdullah NMA, Jamal R, Abu N
    Sci Rep, 2019 Nov 11;9(1):16497.
    PMID: 31712601 DOI: 10.1038/s41598-019-53063-y
    Chemo-resistance is associated with poor prognosis in colorectal cancer (CRC), with the absence of early biomarker. Exosomes are microvesicles released by body cells for intercellular communication. Circular RNAs (circRNAs) are non-coding RNAs with covalently closed loops and enriched in exosomes. Crosstalk between circRNAs in exosomes and chemo-resistance in CRC remains unknown. This research aims to identify exosomal circRNAs associated with FOLFOX-resistance in CRC. FOLFOX-resistant HCT116 CRC cells (HCT116-R) were generated from parental HCT116 cells (HCT116-P) using periodic drug induction. Exosomes were characterized using transmission electron microscopy (TEM), Zetasizer and Western blot. Our exosomes were translucent cup-shaped structures under TEM with differential expression of TSG101, CD9, and CD63. We performed circRNAs microarray using exosomal RNAs from HCT116-R and HCT116-P cells. We validated our microarray data using serum samples. We performed drug sensitivity assay and cell cycle analysis to characterize selected circRNA after siRNA-knockdown. Using fold change >2 and p 
  19. Fulltext MicroRNA-200c and microRNA-31 regulate proliferation, colony formation, migration and invasion in serous ovarian cancer
    Ibrahim FF, Jamal R, Syafruddin SE, Ab Mutalib NS, Saidin S, MdZin RR, et al.
    J Ovarian Res, 2015;8:56.
    PMID: 26260454 DOI: 10.1186/s13048-015-0186-7
    Serous epithelial ovarian cancer (SEOC) is a highly metastatic disease and its progression has been implicated with microRNAs. This study aimed to identify the differentially expressed microRNAs in Malaysian patients with SEOC and examine the microRNAs functional roles in SEOC cells.
  20. Fulltext Circular RNAs: Potential Regulators of Treatment Resistance in Human Cancers
    Jeyaraman S, Hanif EAM, Ab Mutalib NS, Jamal R, Abu N
    Front Genet, 2019;10:1369.
    PMID: 32047511 DOI: 10.3389/fgene.2019.01369
    Circular RNAs (circRNAs) which were once considered as "junk" are now in the spotlight as a potential player in regulating human diseases, especially cancer. With the development of high throughput technologies in recent years, the full potential of circRNAs is being uncovered. CircRNAs possess some unique characteristics and advantageous properties that could benefit medical research and clinical applications. CircRNAs are stable with covalently closed loops that are resistant to ribonucleases, have disease stage-specific expressions and are selectively abundant in different types of tissues. Interestingly, the presence of circRNAs in different types of treatment resistance in human cancers was recently observed with the involvement of a few key pathways. The activation of certain pathways by circRNAs may give new insights to treatment resistance management. The potential usage of circRNAs from this aspect is very much in its infancy stage and has not been fully validated. This mini-review attempts to highlight the possible role of circRNAs as regulators of treatment resistance in human cancers based on its intersection molecules and cancer-related regulatory networks.
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