Displaying publications 1 - 20 of 28 in total

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  1. Fulltext Revisiting the Roles of Pro-Metastatic EpCAM in Cancer
    Mohtar MA, Syafruddin SE, Nasir SN, Low TY
    Biomolecules, 2020 02 07;10(2).
    PMID: 32046162 DOI: 10.3390/biom10020255
    Epithelial cell adhesion molecule (EpCAM) is a cell surface protein that was discovered as a tumour marker of epithelial origins nearly four decades ago. EpCAM is expressed at basal levels in the basolateral membrane of normal epithelial cells. However, EpCAM expression is upregulated in solid epithelial cancers and stem cells. EpCAM can also be found in disseminated tumour cells and circulating tumour cells. Various OMICs studies have demonstrated that EpCAM plays roles in several key biological processes such as cell adhesion, migration, proliferation and differentiation. Additionally, EpCAM can be detected in the bodily fluid of cancer patients suggesting that EpCAM is a pathophysiologically relevant anti-tumour target as well as being utilized as a diagnostic/prognostic agent for a variety of cancers. This review will focus on the structure-features of EpCAM protein and discuss recent evidence on the pathological and physiological roles of EpCAM in modulating cell adhesion and signalling pathways in cancers as well as deliberating the clinical implication of EpCAM as a therapeutic target.
  2. Fulltext Interleukin-1 alpha and high mobility group box-1 secretion in polyinosinic:polycytidylic-induced colorectal cancer cells occur via RIPK1-dependent mechanism and participate in tumourigenesis
    Cheng KJ, Mohamed EHM, Syafruddin SE, Ibrahim ZA
    J Cell Commun Signal, 2023 Mar;17(1):189-208.
    PMID: 35534784 DOI: 10.1007/s12079-022-00681-3
    Pathogenic infections have significant roles in the pathogenesis of colorectal cancer (CRC). These infections induce the secretion of various damage-associated molecular patterns (DAMPs) including interleukin-1 alpha (IL-1α) and high mobility group box-1 (HMGB1). Despite their implication in CRC pathogenesis, the mechanism(s) that modulate the secretion of IL-1α and HMGB1, along with their roles in promoting CRC tumourigenesis remain poorly understood. To understand the secretory mechanism, HT-29 and SW480 cells were stimulated with infectious mimetics; polyinosinic:polycytidylic acid [Poly(I:C)], lipopolysaccharide (LPS) and pro-inflammatory stimuli; tumour necrosis factor-alpha (TNF-α). IL-1α and HMGB1 secretion levels upon stimulation were determined via ELISA. Mechanism(s) mediating IL-1α and HMGB1 secretion in CRC cells were characterized using pharmacological inhibitors and CRISPR-Cas9 gene editing targeting relevant pathways. Recombinant IL-1α and HMGB1 were utilized to determine their impact in modulating pro-tumourigenic properties of CRC cells. Pharmacological inhibition showed that Poly(I:C)-induced IL-1α secretion was mediated through endoplasmic reticulum (ER) stress and RIPK1 signalling pathway. The secretion of HMGB1 was RIPK1-dependent but independent of ER stress. RIPK1-targeted CRC cell pools exhibited decreased cell viability upon Poly(I:C) stimulation, suggesting a potential role of RIPK1 in CRC cells survival. IL-1α has both growth-promoting capabilities and stimulates the production of pro-metastatic mediators, while HMGB1 only exhibits the latter; with its redox status having influence. We demonstrated a potential role of RIPK1-dependent signalling pathway in mediating the secretion of IL-1α and HMGB1 in CRC cells, which in turn enhances CRC tumorigenesis. RIPK1, IL-1α and HMGB1 may serve as potential therapeutic targets to mitigate CRC progression.
  3. Fulltext More Than Meets the Eye: Revisiting the Roles of Heat Shock Factor 4 in Health and Diseases
    Syafruddin SE, Ling S, Low TY, Mohtar MA
    Biomolecules, 2021 Mar 31;11(4).
    PMID: 33807297 DOI: 10.3390/biom11040523
    Cells encounter a myriad of endogenous and exogenous stresses that could perturb cellular physiological processes. Therefore, cells are equipped with several adaptive and stress-response machinery to overcome and survive these insults. One such machinery is the heat shock response (HSR) program that is governed by the heat shock factors (HSFs) family in response towards elevated temperature, free radicals, oxidants, and heavy metals. HSF4 is a member of this HSFs family that could exist in two predominant isoforms, either the transcriptional repressor HSFa or transcriptional activator HSF4b. HSF4 is constitutively active due to the lack of oligomerization negative regulator domain. HSF4 has been demonstrated to play roles in several physiological processes and not only limited to regulating the classical heat shock- or stress-responsive transcriptional programs. In this review, we will revisit and delineate the recent updates on HSF4 molecular properties. We also comprehensively discuss the roles of HSF4 in health and diseases, particularly in lens cell development, cataract formation, and cancer pathogenesis. Finally, we will posit the potential direction of HSF4 future research that could enhance our knowledge on HSF4 molecular networks as well as physiological and pathophysiological functions.
  4. Fulltext Cholesterol accumulation in ccRCC: the role of ccRCC-initiating VHL-HIFα pathway
    Mohtar MA, Hasanah Mohd Yusuf SN, Syafruddin SE
    EBioMedicine, 2024 Apr 09;103:105112.
    PMID: 38599011 DOI: 10.1016/j.ebiom.2024.105112
  5. Secretion of pro-oncogenic AGR2 protein in cancer
    Moidu NA, A Rahman NS, Syafruddin SE, Low TY, Mohtar MA
    Heliyon, 2020 Sep;6(9):e05000.
    PMID: 33005802 DOI: 10.1016/j.heliyon.2020.e05000
    Anterior gradient-2 (AGR2) protein mediates the formation, breakage and isomerization of disulphide bonds during protein maturation in the endoplasmic reticulum (ER) and contributes to the homoeostasis of the secretory pathway. AGR2 promotes tumour development and metastasis and its elevated expression is almost completely restricted to malignant tumours. Interestingly, this supposedly ER-resident protein can be localised to other compartments of cancer cells and can also be secreted into the extracellular milieu. There are emerging evidences that describe the gain-of-function activities of the extracellular AGR2, particularly in cancer development. Here, we reviewed studies detailing the expression, pathological and physiological roles associated with AGR2 and compared the duality of localization, intracellular and extracellular, with special emphasis on the later. We also discussed the possible mechanisms of AGR2 secretion as well as deliberating the functional impacts of AGR2 in cancer settings. Last, we deliberate the current therapeutic strategies and posit the potential use AGR2, as a prognosis and diagnosis marker in cancer.
  6. Fulltext Endogenous HIF2A reporter systems for high-throughput functional screening
    Zaini MN, Patel SA, Syafruddin SE, Rodrigues P, Vanharanta S
    Sci Rep, 2018 08 13;8(1):12063.
    PMID: 30104738 DOI: 10.1038/s41598-018-30499-2
    Tissue-specific transcriptional programs control most biological phenotypes, including disease states such as cancer. However, the molecular details underlying transcriptional specificity is largely unknown, hindering the development of therapeutic approaches. Here, we describe novel experimental reporter systems that allow interrogation of the endogenous expression of HIF2A, a critical driver of renal oncogenesis. Using a focused CRISPR-Cas9 library targeting chromatin regulators, we provide evidence that these reporter systems are compatible with high-throughput screening. Our data also suggests redundancy in the control of cancer type-specific transcriptional traits. Reporter systems such as those described here could facilitate large-scale mechanistic dissection of transcriptional programmes underlying cancer phenotypes, thus paving the way for novel therapeutic approaches.
  7. Fulltext CRISPR Gene-Editing Models Geared Toward Therapy for Hereditary and Developmental Neurological Disorders
    Wong PK, Cheah FC, Syafruddin SE, Mohtar MA, Azmi N, Ng PY, et al.
    Front Pediatr, 2021;9:592571.
    PMID: 33791256 DOI: 10.3389/fped.2021.592571
    Hereditary or developmental neurological disorders (HNDs or DNDs) affect the quality of life and contribute to the high mortality rates among neonates. Most HNDs are incurable, and the search for new and effective treatments is hampered by challenges peculiar to the human brain, which is guarded by the near-impervious blood-brain barrier. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), a gene-editing tool repurposed from bacterial defense systems against viruses, has been touted by some as a panacea for genetic diseases. CRISPR has expedited the research into HNDs, enabling the generation of in vitro and in vivo models to simulate the changes in human physiology caused by genetic variation. In this review, we describe the basic principles and workings of CRISPR and the modifications that have been made to broaden its applications. Then, we review important CRISPR-based studies that have opened new doors to the treatment of HNDs such as fragile X syndrome and Down syndrome. We also discuss how CRISPR can be used to generate research models to examine the effects of genetic variation and caffeine therapy on the developing brain. Several drawbacks of CRISPR may preclude its use at the clinics, particularly the vulnerability of neuronal cells to the adverse effect of gene editing, and the inefficiency of CRISPR delivery into the brain. In concluding the review, we offer some suggestions for enhancing the gene-editing efficacy of CRISPR and how it may be morphed into safe and effective therapy for HNDs and other brain disorders.
  8. Fulltext Integration of RNA-Seq and proteomics data identifies glioblastoma multiforme surfaceome signature
    Syafruddin SE, Nazarie WFWM, Moidu NA, Soon BH, Mohtar MA
    BMC Cancer, 2021 Jul 23;21(1):850.
    PMID: 34301218 DOI: 10.1186/s12885-021-08591-0
    BACKGROUND: Glioblastoma multiforme (GBM) is a highly lethal, stage IV brain tumour with a prevalence of approximately 2 per 10,000 people globally. The cell surface proteins or surfaceome serve as information gateway in many oncogenic signalling pathways and are important in modulating cancer phenotypes. Dysregulation in surfaceome expression and activity have been shown to promote tumorigenesis. The expression of GBM surfaceome is a case in point; OMICS screening in a cell-based system identified that this sub-proteome is largely perturbed in GBM. Additionally, since these cell surface proteins have 'direct' access to drugs, they are appealing targets for cancer therapy. However, a comprehensive GBM surfaceome landscape has not been fully defined yet. Thus, this study aimed to define GBM-associated surfaceome genes and identify key cell-surface genes that could potentially be developed as novel GBM biomarkers for therapeutic purposes.

    METHODS: We integrated the RNA-Seq data from TCGA GBM (n = 166) and GTEx normal brain cortex (n = 408) databases to identify the significantly dysregulated surfaceome in GBM. This was followed by an integrative analysis that combines transcriptomics, proteomics and protein-protein interaction network data to prioritize the high-confidence GBM surfaceome signature.

    RESULTS: Of the 2381 significantly dysregulated genes in GBM, 395 genes were classified as surfaceome. Via the integrative analysis, we identified 6 high-confidence GBM molecular signature, HLA-DRA, CD44, SLC1A5, EGFR, ITGB2, PTPRJ, which were significantly upregulated in GBM. The expression of these genes was validated in an independent transcriptomics database, which confirmed their upregulated expression in GBM. Importantly, high expression of CD44, PTPRJ and HLA-DRA is significantly associated with poor disease-free survival. Last, using the Drugbank database, we identified several clinically-approved drugs targeting the GBM molecular signature suggesting potential drug repurposing.

    CONCLUSIONS: In summary, we identified and highlighted the key GBM surface-enriched repertoires that could be biologically relevant in supporting GBM pathogenesis. These genes could be further interrogated experimentally in future studies that could lead to efficient diagnostic/prognostic markers or potential treatment options for GBM.

  9. Fulltext Two Sides of the Same Coin: The Roles of KLF6 in Physiology and Pathophysiology
    Syafruddin SE, Mohtar MA, Wan Mohamad Nazarie WF, Low TY
    Biomolecules, 2020 09 28;10(10).
    PMID: 32998281 DOI: 10.3390/biom10101378
    The Krüppel-like factors (KLFs) family of proteins control several key biological processes that include proliferation, differentiation, metabolism, apoptosis and inflammation. Dysregulation of KLF functions have been shown to disrupt cellular homeostasis and contribute to disease development. KLF6 is a relevant example; a range of functional and expression assays suggested that the dysregulation of KLF6 contributes to the onset of cancer, inflammation-associated diseases as well as cardiovascular diseases. KLF6 expression is either suppressed or elevated depending on the disease, and this is largely due to alternative splicing events producing KLF6 isoforms with specialised functions. Hence, the aim of this review is to discuss the known aspects of KLF6 biology that covers the gene and protein architecture, gene regulation, post-translational modifications and functions of KLF6 in health and diseases. We put special emphasis on the equivocal roles of its full-length and spliced variants. We also deliberate on the therapeutic strategies of KLF6 and its associated signalling pathways. Finally, we provide compelling basic and clinical questions to enhance the knowledge and research on elucidating the roles of KLF6 in physiological and pathophysiological processes.
  10. Cancer Cell-Derived PDGFB Stimulates mTORC1 Activation in Renal Carcinoma
    Abuhamad AY, Mohamad Zamberi NN, Vanharanta S, Mohd Yusuf SNH, Mohtar MA, Syafruddin SE
    Int J Mol Sci, 2023 Mar 29;24(7).
    PMID: 37047421 DOI: 10.3390/ijms24076447
    Clear cell renal cell carcinoma (ccRCC) is a hypervascular tumor that is characterized by bi-allelic inactivation of the VHL tumor suppressor gene and mTOR signalling pathway hyperactivation. The pro-angiogenic factor PDGFB, a transcriptional target of super enhancer-driven KLF6, can activate the mTORC1 signalling pathway in ccRCC. However, the detailed mechanisms of PDGFB-mediated mTORC1 activation in ccRCC have remained elusive. Here, we investigated whether ccRCC cells are able to secrete PDGFB into the extracellular milieu and stimulate mTORC1 signalling activity. We found that ccRCC cells secreted PDGFB extracellularly, and by utilizing KLF6- and PDGFB-engineered ccRCC cells, we showed that the level of PDGFB secretion was positively correlated with the expression of intracellular KLF6 and PDGFB. Moreover, the reintroduction of either KLF6 or PDGFB was able to sustain mTORC1 signalling activity in KLF6-targeted ccRCC cells. We further demonstrated that conditioned media of PDGFB-overexpressing ccRCC cells was able to re-activate mTORC1 activity in KLF6-targeted cells. In conclusion, cancer cell-derived PDGFB can mediate mTORC1 signalling pathway activation in ccRCC, further consolidating the link between the KLF6-PDGFB axis and the mTORC1 signalling pathway activity in ccRCC.
  11. The Promises and Pitfalls of CRISPR-Mediated Base Editing in Stem Cells
    Wong PK, Mohamad Zamberi NN, Syafruddin SE, Cheah FC, Azmi N, Law JX, et al.
    CRISPR J, 2023 Jun;6(3):196-215.
    PMID: 37219623 DOI: 10.1089/crispr.2023.0013
    Stem cells such as induced pluripotent stem cells, embryonic stem cells, and hematopoietic stem and progenitor cells are growing in importance in disease modeling and regenerative medicine. The applications of CRISPR-based gene editing to create a mélange of disease and nondisease stem cell lines have further enhanced the utility of this innately versatile group of cells in the studies of human genetic disorders. Precise base edits can be achieved using a variety of CRISPR-centric approaches, particularly homology-directed repair and the recently developed base editors and prime editors. Despite its much-touted potential, editing single DNA bases is technically challenging. In this review, we discuss the strategies for achieving exact base edits in the creation of various stem cell-based models for use in elucidating disease mechanisms and assessing drug efficacy, and the unique characteristics of stem cells that warrant special considerations.
  12. dCas9 Tells Tales: Probing Gene Function and Transcription Regulation in Cancer
    Mohamad Zamberi NN, Abuhamad AY, Low TY, Mohtar MA, Syafruddin SE
    CRISPR J, 2024 Apr;7(2):73-87.
    PMID: 38635328 DOI: 10.1089/crispr.2023.0078
    Clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing is evolving into an essential tool in the field of biological and medical research. Notably, the development of catalytically deactivated Cas9 (dCas9) enzyme has substantially broadened its traditional boundaries in gene editing or perturbation. The conjugation of dCas9 with various molecular effectors allows precise control over transcriptional processes, epigenetic modifications, visualization of chromosomal dynamics, and several other applications. This expanded repertoire of CRISPR-Cas9 applications has emerged as an invaluable molecular tool kit that empowers researchers to comprehensively interrogate and gain insights into health and diseases. This review delves into the advancements in Cas9 protein engineering, specifically on the generation of various dCas9 tools that have significantly enhanced the CRISPR-based technology capability and versatility. We subsequently discuss the multifaceted applications of dCas9, especially in interrogating the regulation and function of genes that involve in supporting cancer pathogenesis. In addition, we also delineate the designing and utilization of dCas9-based tools as well as highlighting its current constraints and transformative potentials in cancer research.
  13. 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.
  14. 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.
  15. Characterizing the genetic risk for type 2 diabetes in a Malaysian multi-ethnic cohort
    Abdullah N, Abdul Murad NA, Attia J, Oldmeadow C, Mohd Haniff EA, Syafruddin SE, et al.
    Diabet Med, 2015 Oct;32(10):1377-84.
    PMID: 25711284 DOI: 10.1111/dme.12735
    AIMS: To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project.
    METHODS: We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups.
    RESULTS: After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance.
    CONCLUSION: This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations.
    Study name: The Malaysian Cohort (TMC) project
  16. Fulltext Recent progress in mass spectrometry-based strategies for elucidating protein-protein interactions
    Low TY, Syafruddin SE, Mohtar MA, Vellaichamy A, A Rahman NS, Pung YF, et al.
    Cell Mol Life Sci, 2021 Jul;78(13):5325-5339.
    PMID: 34046695 DOI: 10.1007/s00018-021-03856-0
    Protein-protein interactions are fundamental to various aspects of cell biology with many protein complexes participating in numerous fundamental biological processes such as transcription, translation and cell cycle. MS-based proteomics techniques are routinely applied for characterising the interactome, such as affinity purification coupled to mass spectrometry that has been used to selectively enrich and identify interacting partners of a bait protein. In recent years, many orthogonal MS-based techniques and approaches have surfaced including proximity-dependent labelling of neighbouring proteins, chemical cross-linking of two interacting proteins, as well as inferring PPIs from the co-behaviour of proteins such as the co-fractionating profiles and the thermal solubility profiles of proteins. This review discusses the underlying principles, advantages, limitations and experimental considerations of these emerging techniques. In addition, a brief account on how MS-based techniques are used to investigate the structural and functional properties of protein complexes, including their topology, stoichiometry, copy number and dynamics, are discussed.
  17. Fulltext Profiling of Differentially Expressed MicroRNAs in Human Umbilical Vein Endothelial Cells Exposed to Hyperglycemia via RNA Sequencing
    Othman NS, Aminuddin A, Zainal Abidin S, Syafruddin SE, Ahmad MF, Mohd Mokhtar N, et al.
    Life (Basel), 2023 May 31;13(6).
    PMID: 37374078 DOI: 10.3390/life13061296
    Hyperglycemia is the hallmark of diabetes mellitus that results in oxidative stress, apoptosis, and diabetic vascular endothelial dysfunction. An increasing number of microRNAs (miRNAs) have been found to be involved in the pathogenesis of diabetic vascular complications. However, there is a limited number of studies that characterize the miRNA profile of endothelial cells exposed to hyperglycemia. Therefore, this study aims to analyze the miRNA profile of human umbilical-vein endothelial cells (HUVECs) exposed to hyperglycemia. HUVECs were divided into two groups: the control (treated with 5.5 mM glucose) and hyperglycemia (treated with 33.3 mM glucose) groups. RNA sequencing identified 17 differentially expressed miRNAs between the groups (p < 0.05). Of these, 4 miRNAs were upregulated, and 13 miRNAs were downregulated. Two of the most differentially expressed miRNAs (novel miR-1133 and miR-1225) were successfully validated with stem-loop qPCR. Collectively, the findings show that there is a differential expression pattern of miRNAs in HUVEC following exposure to hyperglycemia. These 17 differentially expressed miRNAs are involved in regulating cellular functions and pathways related to oxidative stress and apoptosis that may contribute to diabetic vascular endothelial dysfunction. The findings provide new clues on the role of miRNAs in the development of diabetic vascular endothelial dysfunction, which could be useful in future targeted therapy.
  18. The spectrum of in vitro maturation in clinical practice: the current insight
    Ahmad MF, Elias MH, Mat Jin N, Abu MA, Syafruddin SE, Zainuddin AA, et al.
    Front Endocrinol (Lausanne), 2023;14:1192180.
    PMID: 37455921 DOI: 10.3389/fendo.2023.1192180
    In vitro oocyte maturation (IVM) has been used worldwide. Despite the long-term implementation, the uptake of this procedure to complement current in vitro fertilization (IVF) remains low. The main reason is likely due to the non-synchronization of protocol and definition criteria, leading to difficulty in collective proper outcome data worldwide and, thus, lack of understanding of the exact IVM procedure. The review aims to consolidate the current clinical practice of IVM by dissecting relevant publications to be tailored for a current spectrum of clinical practice. Nevertheless, the background theories of oocyte maturation were also explored to provide a comprehensive understanding of the basis of IVM theories. Additional discussion of other potential uses of IVM in the future, such as in ovarian tissue cryopreservation known as OTO-IVM for fertility preservation and among women with diminished ovarian reserve, was also explored. Otherwise, future collaboration among all IVM centers is paramount for better collection of clinical data to provide valid recommendations for IVM in clinical practice, especially in molecular integrity and possible DNA alteration if present for IVM offspring outcome safety purposes.
  19. Fulltext Expression of HOXA10 Gene in Women with Endometriosis: A Systematic Review
    Lazim N, Elias MH, Sutaji Z, Abdul Karim AK, Abu MA, Ugusman A, et al.
    Int J Mol Sci, 2023 Aug 17;24(16).
    PMID: 37629050 DOI: 10.3390/ijms241612869
    The homeobox A10 (HOXA10) gene is known to be related to endometriosis; however, due to a lack of knowledge/evidence in the pathogenesis of endometriosis, the mechanisms that link HOXA10 to endometriosis still need to be clarified. This review addresses the difference in the expression of the HOXA10 gene in endometriotic women versus non-endometriotic women across populations by country and discusses its influences on women's fertility. An organized search of electronic databases was conducted in Scopus, ScienceDirect, PubMed, and Web of Science. The keywords used were (HOXA10 OR "homeobox A10" OR PL OR HOX1 OR HOX1H OR HOX1.8) AND ("gene expression") AND (endometriosis). The initial search resulted in 623 articles, 10 of which were included in this review. All ten papers included in this study were rated fair in terms of the quality of the studies conducted. The expression of the HOXA10 gene was found to be downregulated in most studies. However, one study provided evidence of the downregulation and upregulation of HOXA10 gene expression due to the localization of endometriotic lesions. Measuring the expression of the HOXA10 gene in women is clinically essential to predicting endometriosis, endometrial receptivity, and the development of pinopodes in the endometrium during the luteal phase.
  20. Fulltext Targeted Next-Generation Sequencing Identifies Actionable Targets in Estrogen Receptor Positive and Estrogen Receptor Negative Endometriod Endometrial Cancer
    Suhaimi SS, Ab Mutalib NS, Khor SS, Zain RRM, Syafruddin SE, Abu N, et al.
    Front Pharmacol, 2018;9:750.
    PMID: 30057548 DOI: 10.3389/fphar.2018.00750
    Endometrioid endometrial cancer (EEC) is the commonest form of endometrial cancer and can be divided into estrogen receptor (ER) positive and negative subtypes. The mutational profiles of EEC have been shown to aid in tailoring treatment; however, little is known about the differences between the gene mutation profiles between these two subtypes. This study aims to investigate the gene mutation profile in ER positive and negative EEC, and to further elucidate the role of WHSC1 mutations in this cancer. EEC and normal endometrial tissues were obtained from 29 patients and subjected to next-generation sequencing (NGS) using Ion Ampliseq Comprehensive Cancer PanelTM targeting 409 cancer related. A total of 741 non-synonymous alterations were identified from 272 genes in ER positive subtype while 448 non-synonymous variants were identified from 221 genes in ER negative subtype. PTEN is the most frequently altered gene in ER positive subtype (64%, 7/11) while ARID1A is the most frequently altered gene in ER negative subtype (50%, 4/8). We also identified alterations in ERRB3 (36%, 4/11), GNAS (36%, 4/11), and WHSC1 (27%, 3/11) in the ER positive subtype. WHSC1 R1126H and L1268P were shown to significantly increase cell viability, proliferation, migration, and survival. In addition, reduction in ER expression sensitized EEC-1 cell with WHSC1 L1268P mutant to Fulvestrant treatment. We revealed the mutational spectra of ER positive and ER negative EEC that could lead to better understanding of the biological mechanisms of endometrial cancer and may ultimately result in improvement of treatment options and patient prognosis.
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