Displaying publications 81 - 100 of 336 in total

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  1. Fulltext FAT1 mutations cause a glomerulotubular nephropathy
    Gee HY, Sadowski CE, Aggarwal PK, Porath JD, Yakulov TA, Schueler M, et al.
    Nat Commun, 2016 Feb 24;7:10822.
    PMID: 26905694 DOI: 10.1038/ncomms10822
    Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function.
    Matched MeSH terms: Cell Movement/genetics*
  2. A novel caryophyllene type sesquiterpene lactone from Asparagus falcatus (Linn.); structure elucidation and anti-angiogenic activity on HUVECs
    Ghalib RM, Hashim R, Sulaiman O, Mehdi SH, Valkonen A, Rissanen K, et al.
    Eur J Med Chem, 2012 Jan;47(1):601-7.
    PMID: 22074984 DOI: 10.1016/j.ejmech.2011.10.037
    In this study the novel caryophyllene type sesquiterpene lactone (aspfalcolide) has been isolated from the leaves of Asparagus falcatus (Linn.) and characterized by IR, 1D NMR, 2D NMR, EI-MS, HR-ESI-MS and X-ray single crystal diffraction analysis. The aspfalcolide crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 6.37360(10), b = 7.6890(2), c = 27.3281(6) Å, α = β = γ = 90(°) and Z = 4. One intermolecular O-H⋯O hydrogen bond enforces these natural molecules to form infinite chains through the crystal. Aspfalcolide was screened for its anti-angiogenic activity in human umbilical vein endothelial cells (HUVECs) and the result showed the remarkable inhibitory effect of aspfalcolide on the proliferation (IC(50) 1.82 μM), migration and tube formation of HUVECs.
    Matched MeSH terms: Cell Movement/drug effects
  3. Fulltext Evaluation of new suspension system for limb prosthetics
    Gholizadeh H, Abu Osman NA, Eshraghi A, Ali S, Arifin N, Wan Abas WA
    Biomed Eng Online, 2014;13:1.
    PMID: 24410918 DOI: 10.1186/1475-925X-13-1
    Good prosthetic suspension system secures the residual limb inside the prosthetic socket and enables easy donning and doffing. This study aimed to introduce, evaluate and compare a newly designed prosthetic suspension system (HOLO) with the current suspension systems (suction, pin/lock and magnetic systems).
    Matched MeSH terms: Movement
  4. γ-Synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to the colon adenocarcinoma LS 174T cell line
    Goh KW, Say YH
    Tumour Biol., 2015 Sep;36(10):7947-60.
    PMID: 25956278 DOI: 10.1007/s13277-015-3455-6
    γ-synuclein, a neuronal protein of the synuclein family, is involved in carcinogenesis. To investigate its role in colorectal cancer carcinogenesis, we overexpressed γ-synuclein in LS 174T colon adenocarcinoma cell line (termed LS 174T-γsyn). When compared with untransfected/mock transfectants, LS 174T-γsyn had higher mobility in scratch wound assay, tend to scatter more in cell-scattering assay, and had enhanced lamellipodia and filopodia formation in cell-spreading assay. Enhanced adhesion of LS 174T-γsyn to fibronectin and collagen and significantly higher proliferation rate showed that γ-synuclein was able to increase extracellular matrix interaction and promoted proliferation of LS 174T. Higher invasiveness of LS 174T-γsyn was evidenced by enhanced invasion to the bottom of the basement membrane in Boyden chamber assay. However, LS 174T-γsyn were significantly more vulnerable to doxorubicin, vincristine and hydrogen peroxide insults, via apoptotic cell death. LS 174T-γsyn also had reduced anchorage-independent growth as shown by reduced colony formation and reduced anoikis resistance. We found that overexpression of γ-synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to LS 174T, where the former was mediated through enhanced cyclic adenosine monophosphate response element binding protein (CREB) phosphorylation, while the latter involved hepatocyte growth factor (HGF) downregulation and subsequent downstream signalling pathways possibly involving extracellular signal-regulated kinases (ERK)1/2, p38α, c-Jun N-terminal kinase (JNK) pan and Signal Transducers and Activators of Transcription (STATs). This unexpected contrasting finding as compared to other similar studies on colon cancer cell lines might be correlated with the degree of tumour advancement from which the cell lines were derived from.
    Matched MeSH terms: Cell Movement/drug effects*
  5. Clinical Activity Monitoring System (CATS): An automatic system to quantify bedside clinical activities in the intensive care unit
    Guo P, Chiew YS, Shaw GM, Shao L, Green R, Clark A, et al.
    Intensive Crit Care Nurs, 2016 Dec;37:52-61.
    PMID: 27401048 DOI: 10.1016/j.iccn.2016.05.003
    Monitoring clinical activity at the bedside in the intensive care unit (ICU) can provide useful information to evaluate nursing care and patient recovery. However, it is labour intensive to quantify these activities and there is a need for an automated method to record and quantify these activities. This paper presents an automated system, Clinical Activity Tracking System (CATS), to monitor and evaluate clinical activity at the patient's bedside. The CATS uses four Microsoft Kinect infrared sensors to track bedside nursing interventions. The system was tested in a simulated environment where test candidates performed different motion paths in the detection area. Two metrics, 'Distance' and 'Dwell time', were developed to evaluate interventions or workload in the detection area. Results showed that the system can accurately track the intervention performed by individual or multiple subjects. The results of a 30-day, 24-hour preliminary study in an ICU bed space matched clinical expectations. It was found that the average 24-hour intervention is 22.0minutes/hour. The average intervention during the day time (7am-11pm) is 23.6minutes/hour, 1.4 times higher than 11pm-7am, 16.8minutes/hour. This system provides a unique approach to automatically collect and evaluate nursing interventions that can be used to evaluate patient acuity and workload demand.
    Matched MeSH terms: Movement
  6. Fulltext Tumor suppressor role of miR-503
    Gupta G, Chellappan DK, de Jesus Andreoli Pinto T, Hansbro PM, Bebawy M, Dua K
    Panminerva Med, 2018 Mar;60(1):17-24.
    PMID: 29164842 DOI: 10.23736/S0031-0808.17.03386-9
    MicroRNAs (miRNAs) are non-coding RNAs of around 20-25 nucleotides in length with highly conserved characteristics. They moderate post-transcriptional silencing by precisely combining with 3' untranslated regions (UTRs) of target mRNAs at a complementary site. miR‑503, an associate of the "canonical" miRNA-16 family, is expressed in numerous types of tumors such as breast cancer, prostate cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, glioblastoma and several others. There is convincing evidence to show that miR‑503 functions as a tumor suppressor gene through its effects on target genes that regulate cell proliferation, migration, and invasion in tumor cells. In this current assessment, we discuss the biology and tumor suppressor role of miR‑503 in different cancers and elaborate on its mechanism of action.
    Matched MeSH terms: Cell Movement
  7. Phosphoinositide 3-kinase δ inactivation prevents vitreous-induced activation of AKT/MDM2/p53 and migration of retinal pigment epithelial cells
    Han H, Chen N, Huang X, Liu B, Tian J, Lei H
    J Biol Chem, 2019 10 18;294(42):15408-15417.
    PMID: 31467081 DOI: 10.1074/jbc.RA119.010130
    Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that play a critical role in transmitting signals from cell-surface molecules to intracellular protein effectors. Key PI3Ks include PI3Kα, PI3Kβ, and PI3Kδ, which are regulated by receptors. The signaling pathway comprising the PI3Ks, along with a Ser/Thr kinase (AKT), a proto-oncogene product (mouse double minute (MDM)2), and a tumor suppressor protein (p53), plays an essential role in experimental proliferative vitreoretinopathy (PVR), which is a fibrotic blinding eye disorder. However, which PI3K isoforms are involved in PVR is unknown. A major characteristic of PVR is the formation of epi (or sub)-retinal membranes that consist of extracellular matrix and cells, including retinal pigment epithelium (RPE) cells, glial cells, and macrophages. RPE cells are considered key players in PVR pathogenesis. Using immunoblotting and immunofluorescence analyses, we herein provide the evidence that PI3Kδ is highly expressed in human RPEs when it is primarily expressed in leukocytes. We also found that PI3Kδ inactivation through two approaches, CRISPR/Cas9-mediated depletion and a PI3Kδ-specific inhibitor (idelalisib), not only blocks vitreous-induced activation of AKT and MDM2 but also abrogates a vitreous-stimulated decrease in p53. Furthermore, we demonstrate that PI3Kδ inactivation prevents vitreous-induced proliferation, migration, and contraction of human RPEs. These results suggest that PI3Kδ may represent a potential therapeutic target for RPE-related eye diseases, including PVR.
    Matched MeSH terms: Cell Movement
  8. Fulltext Capilliposide B blocks VEGF-induced angiogenesis in vitro in primary human retinal microvascular endothelial cells
    Han H, Yang Y, Wu Z, Liu B, Dong L, Deng H, et al.
    Biomed Pharmacother, 2021 Jan;133:110999.
    PMID: 33227710 DOI: 10.1016/j.biopha.2020.110999
    Abnormal angiogenesis is associated with intraocular diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, and current therapies for these eye diseases are not satisfactory. The purpose of this study was to determine whether capilliposide B (CPS-B), a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl, can inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis signaling events and cellular responses in primary human retinal microvascular endothelial cells (HRECs). Our study revealed that the capilliposide B IC50 for HRECs was 8.5 μM at 72 h and that 1 μM capilliposide B specifically inhibited VEGF-induced activation of VEGFR2 and its downstream signaling enzymes Akt and Erk. In addition, we discovered that this chemical effectively blocked VEGF-stimulated proliferation, migration and tube formation of the HRECs, suggesting that capilliposide B is a promising prophylactic for angiogenesis-associated diseases such as proliferative diabetic retinopathy.
    Matched MeSH terms: Cell Movement/drug effects
  9. Fulltext The Rajakumar Movement
    Harris N P
    Malays Fam Physician, 2009;4(1):6-7.
    Note by TCL: The Rajakumar Movement is the Wonca Asia Pacific Region Working Party for Young and Future Family Doctors. It was named in honour of Dr M K Rajakumar.
    Matched MeSH terms: Movement
  10. Fulltext The Molecular Targets and Anti-Invasive Effects of 2,6-bis-(4-hydroxyl-3methoxybenzylidine) cyclohexanone or BHMC in MDA-MB-231 Human Breast Cancer Cells
    Harun SNA, Israf DA, Tham CL, Lam KW, Cheema MS, Md Hashim NF
    Molecules, 2018 Apr 10;23(4).
    PMID: 29642589 DOI: 10.3390/molecules23040865
    In order to metastasize, tumor cells need to migrate and invade the surrounding tissues. It is important to identify compound(s) capable of disrupting the metastasis of invasive cancer cells, especially for hindering invadopodia formation, so as to provide anti-metastasis targeted therapy. Invadopodia are thought to be specialized actin-rich protrusions formed by highly invasive cancer cells to degrade the extracellular matrix (ECM). A curcuminoid analogue known as 2,6-bis-(4-hydroxy-3-methoxybenzylidine)cyclohexanone or BHMC has shown good potential in inhibiting inflammation and hyperalgesia. It also possesses an anti-tumor effects on 4T1 murine breast cancer cells in vivo. However, there is still a lack of empirical evidence on how BHMC works in preventing human breast cancer invasion. In this study, we investigated the effect of BHMC on MDA-MB-231 breast cancer cells and its underlying mechanism of action to prevent breast cancer invasion, especially during the formation of invadopodia. All MDA-MB-231 cells, which were exposed to the non-cytotoxic concentrations of BHMC, expressed the proliferating cell nuclear antigen (PCNA), which indicate that the anti-proliferative effects of BHMC did not interfere in the subsequent experiments. By using a scratch migration assay, transwell migration and invasion assays, we determined that BHMC reduces the percentage of migration and invasion of MDA-MB-231 cells. The gelatin degradation assay showed that BHMC reduced the number of cells with invadopodia. Analysis of the proteins involved in the invasion showed that there is a significant reduction in the expressions of Rho guanine nucleotide exchange factor 7 (β-PIX), matrix metalloproteinase-9 (MMP-9), and membrane type 1 matrix metalloproteinase (MT1-MMP) in the presence of BHMC treatment at 12.5 µM. Therefore, it can be postulated that BHMC at 12.5 µM is the optimal concentration for preventing breast cancer invasion.
    Matched MeSH terms: Cell Movement/drug effects
  11. Compression and texture in socks enhance football kicking performance
    Hasan H, Davids K, Chow JY, Kerr G
    Hum Mov Sci, 2016 Aug;48:102-11.
    PMID: 27155962 DOI: 10.1016/j.humov.2016.04.008
    The purpose of this study was to observe effects of wearing textured insoles and clinical compression socks on organisation of lower limb interceptive actions in developing athletes of different skill levels in association football. Six advanced learners and six completely novice football players (15.4±0.9years) performed 20 instep kicks with maximum velocity, in four randomly organised insoles and socks conditions, (a) Smooth Socks with Smooth Insoles (SSSI); (b) Smooth Socks with Textured Insoles (SSTI); (c) Compression Socks with Smooth Insoles (CSSI) and (d), Compression Socks with Textured Insoles (CSTI). Reflective markers were placed on key anatomical locations and the ball to facilitate three-dimensional (3D) movement recording and analysis. Data on 3D kinematic variables and initial ball velocity were analysed using one-way mixed model ANOVAs. Results revealed that wearing textured and compression materials enhanced performance in key variables, such as the maximum velocity of the instep kick and increased initial ball velocity, among advanced learners compared to the use of non-textured and compression materials. Adding texture to football boot insoles appeared to interact with compression materials to improve kicking performance, captured by these important measures. This improvement in kicking performance is likely to have occurred through enhanced somatosensory system feedback utilised for foot placement and movement organisation of the lower limbs. Data suggested that advanced learners were better at harnessing the augmented feedback information from compression and texture to regulate emerging movement patterns compared to novices.
    Matched MeSH terms: Movement/physiology
  12. Chemotherapeutic potentials of the stem bark of Balanite aegyptiaca (L.) Delile: an antiangiogenic, antitumor and antioxidant agent
    Hassan LE, Dahham SS, Saghir SA, Mohammed AM, Eltayeb NM, Majid AM, et al.
    BMC Complement Altern Med, 2016 Oct 19;16(1):396.
    PMID: 27760539
    Balanite aegyptiaca (L.) Delile, is a plant with extensive medicinal properties. Its stem bark is traditionally known for its spasmolytic and antiepileptic properties and used to treat yellow fever, jaundice and syphilis. Angiogenesis (sprouting of new blood vessels) is crucial for tumor growth and metastasis. The goal of this study is investigate the antiangiogenic, cytotoxicity and antioxidant activity as well as antitumor in vivo properties of B. aegyptiaca stem bark extracts.
    Matched MeSH terms: Cell Movement/drug effects
  13. Fulltext Preparation, characterization and therapeutic properties of gum arabic-stabilized gallic acid nanoparticles
    Hassani A, Azarian MMS, Ibrahim WN, Hussain SA
    Sci Rep, 2020 10 20;10(1):17808.
    PMID: 33082415 DOI: 10.1038/s41598-020-71175-8
    Gallic acid (GA) is a natural phenolic compound with therapeutic effects that are often challenged by its rapid metabolism and clearance. Therefore,  GA was encapsulated using gum arabic into nanoparticles to increase its bioavailability. The formulated nanoparticles (GANPs) were characterized for physicochemical properties and size and were then evaluated for antioxidant and antihypertensive effects using various established in vitro assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging (NO), β-carotene bleaching and angiotensin-converting enzyme (ACE) inhibitory assays. The GANPs were further evaluated for the in vitro cytotoxicity, cell uptake and cell migration in four types of human cancer cell lines including (MCF-7, MDA-MB231) breast adenocarcinoma, HepG2 hepatocellular cancer, HT-29 colorectal adenocarcinoma, and MCF-10A breast epithelial cell lines. The GANPs demonstrated potent antioxidant effects and have shown promising anti-cancer properties in a dose-dependent manner with a predilection toward HepG2 and MCF7 cancer cells. The uptake of GANPs was successful in the majority of cancer cells with a propensity to accumulate in the nuclear region of the cells. The HepG2 and MCF7 cancer cells also had a significantly higher percentage of apoptosis and were more sensitive to gallic acid nanoparticle treatment in the cell migration assay. This study is the first to confirm the synergistic effects of gum arabic in the encapsulation of gallic acid by increasing the selectivity towards cancer cells and enhancing  the antioxidant properties. The formulated nanoparticles also had remarkably low toxicity in normal cells. Based on these findings, GANPs may have promising therapeutic applications towards the development of more effective treatments with a probable targeting precision in cancer cells.
    Matched MeSH terms: Cell Movement
  14. Expression of AR, 5αR1 and 5αR2 in bladder urothelial carcinoma and relationship to clinicopathological factors
    Hata S, Ise K, Azmahani A, Konosu-Fukaya S, McNamara KM, Fujishima F, et al.
    Life Sci, 2017 Dec 01;190:15-20.
    PMID: 28947209 DOI: 10.1016/j.lfs.2017.09.029
    AIMS: Bladder urothelial carcinoma is increasing in incidence with age and its prognosis could become worse when accompanied with metastasis. Effective treatment of these advanced patients is required and it becomes important to understand its underlying biology of this neoplasm, especially with regard to its biological pathways. A potential proposed pathway is androgen receptor (AR)-mediated intracellular signaling but the details have remained relatively unexplored.

    MAIN METHODS: The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT).

    KEY FINDINGS: DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity.

    SIGNIFICANCE: Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior.

    Matched MeSH terms: Cell Movement/genetics
  15. Fulltext Parvimonas micra infection enhances proliferation, wound healing, and inflammation of a colorectal cancer cell line
    Hatta MNA, Mohamad Hanif EA, Chin SF, Low TY, Neoh HM
    Biosci Rep, 2023 Jun 28;43(6).
    PMID: 37218575 DOI: 10.1042/BSR20230609
    The gut microbiota Parvimonas micra has been found to be enriched in gut mucosal tissues and fecal samples of colorectal cancer (CRC) patients compared with non-CRC controls. In the present study, we investigated the tumorigenic potential of P. micra and its regulatory pathways in CRC using HT-29, a low-grade CRC intestinal epithelial cell. For every P. micra-HT-29 interaction assay, HT-29 was co-cultured anaerobically with P. micra at an MOI of 100:1 (bacteria: cells) for 2 h. We found that P. micra increased HT-29 cell proliferation by 38.45% (P=0.008), with the highest wound healing rate at 24 h post-infection (P=0.02). In addition, inflammatory marker expression (IL-5, IL-8, CCL20, and CSF2) was also significantly induced. Shotgun proteomics profiling analysis revealed that P. micra affects the protein expression of HT-29 (157 up-regulated and 214 down-regulated proteins). Up-regulation of PSMB4 protein and its neighbouring subunits revealed association of the ubiquitin-proteasome pathway (UPP) in CRC carcinogenesis; whereas down-regulation of CUL1, YWHAH, and MCM3 signified cell cycle dysregulation. Moreover, 22 clinically relevant epithelial-mesenchymal transition (EMT)-markers were expressed in HT-29 infected with P. micra. Overall, the present study elucidated exacerbated oncogenic properties of P. micra in HT-29 via aberrant cell proliferation, enhanced wound healing, inflammation, up-regulation of UPPs, and activation of EMT pathways.
    Matched MeSH terms: Cell Movement
  16. Fulltext Motor neurological soft signs among patients with Schizophrenia: a clinical significance
    Hazli Zakaria, Nik Ruzyanei Nik Jaafar, Azlin Baharudin, Normala Ibrahim, Marhani Midin
    Sains Malaysiana, 2013;42(3):381-388.
    Neurological soft signs (NSS) are subtle indicators of brain dysfunction which are present in excess among patients with Schizophrenia. Its clinical significance remains unclear despite extensive researches in this area. The objective of this work was to determine the proportion of schizophrenia patients who have motor NSS and then to compare the clinical features between these two groups; with and without motor NSS. This cross-sectional study which utilized the brief motor scale (BMS) was used to investigate the presence of motor NSS in 80 schizophrenia patients who attended Universiti Kebangsaan Malaysia Medical Centre (UKMCC) Psychiatric clinic. The diagnosis of schizophrenia was confirmed by mini international neuropsychiatic interview (MINI). Symptomatology and abnormal motor movement were assessed using the brief psychiatric rating scale (BPRS) and abnormal involuntary movement scale (AIMS), respectively. A brief battery of cognitive tests covering aspects of attention, working memory and executive function was administered. The bivariate analyses were applied to look for any relationship between the study factors. Majority of schizophrenia patients (68.8%) in this study have motor NSS. The motor NSS were associated with ethnic group, level of education, age of onset, duration of illness and performance in cognitive assessment; verbal fluency, digit span forward, digit span backward
    and trail making B (p<0.05) but not with trail making A. The assessment of motor NSS represents a brief, inexpensive and meaningful tool in assessing the cognitive functions in schizophrenia. It has the potential as an illness marker and a link between neurobiological research and clinical practice.
    Matched MeSH terms: Abnormal Involuntary Movement Scale
  17. Inhibition of cell migration and invasion by miR‑29a‑3p in a colorectal cancer cell line through suppression of CDC42BPA mRNA expression
    He PY, Yip WK, Chai BL, Chai BY, Jabar MF, Dusa N, et al.
    Oncol Rep, 2017 Dec;38(6):3554-3566.
    PMID: 29039592 DOI: 10.3892/or.2017.6037
    The objective of this study was to determine the effect of miR‑29a‑3p inhibitor on the migration and invasion of colorectal cancer cell lines (CRC) and the underlying molecular mechanisms. miR‑29a‑3p was detected using reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) in the CRC cell lines HCT11, CaCo2, HT29, SW480 and SW620. An invasive subpopulation designated SW480‑7 was derived from the parental cell line, detected by Transwell and Transwell Matrigel assays. Cytoskeleton Regulators RT2 profiler PCR array and western blot analysis were utilized to identify the alterations in expression of downstream mRNAs. siRNA against CDC42BPA was transfected into SW480‑7 and effects on cell migration and invasion were investigated. Data obtained showed that miR‑29a‑3p was detected in these five CRC cell lines. miR‑29a‑3p inhibitor had no effect on viability but stimulated cell migration and invasion of SW480‑7 cells. In contrast, miR‑29a‑3p mimic suppressed cell migration and invasion. TargetScan miRBD and DIANA were employed to identify the potential direct target genes of miR‑29a‑3p in the Cytoskeleton Regulators RT2-Profiler PCR array. Cytoskeleton Regulators RT2-Profiler PCR array data showed that 3 out of the 5 predicted targets genes, CDC42BPA (2.33-fold), BAIAP2 (1.79-fold) and TIAM1 (1.77-fold), in the array were upregulated by miR‑29a‑3p. A significant increase in expression IQGAP2, PHLDB2, SSH1 mRNAs and downregulation of PAK1 mRNA was also detected with miR‑29a‑3p inhibition. Increase in CDC42BPA, SSH1 and IQGAP2 mRNA expression correlated with increased protein level in miR‑29a‑3p transfected SW-480-7 cells. Silencing of CDC42BPA (an enhancer of cell motility) partially abolished miR‑29a‑3p inhibitor-induced stimulation of cell migration and invasion. miR‑29a‑3p expression in stage II and III CRC is relatively lower than that of stage I CRC. However, the data need to be interpreted with caution due to the small sample size. In conclusion, inhibition of miR‑29a‑3p stimulates SW480‑7 cell migration and invasion and downstream expression IQGAP2, PHLDB2, SSH1 mRNAs are upregulated whilst PAK1 mRNA is downregulated. Silencing of CDC42BPA expression partially reduces miR29a‑3p inhibitor-induced migration and invasion of SW480‑7 cells.
    Matched MeSH terms: Cell Movement
  18. Fulltext Effect of the miR-96-5p inhibitor and mimic on the migration and invasion of the SW480-7 colorectal cancer cell line
    He PY, Yip WK, Jabar MF, Mohtarrudin N, Dusa NM, Seow HF
    Oncol Lett, 2019 Aug;18(2):1949-1960.
    PMID: 31423265 DOI: 10.3892/ol.2019.10492
    The objectives of the present study were to identify the aberrant expression of microRNA (miRNA) in colorectal carcinoma (CRC) tissues from published miRNA profiling studies and to investigate the effects of the identified miRNA inhibitor and mimic miR-96-5p on CRC cell migration and invasion. The altered expression of the regulators of cytoskeleton mRNA in miR-96-5p inhibitor-transfected cells was determined. The miR-96-5p expression level in five CRC cell lines, HCT11, CaCo2, HT29, SW480 and SW620, and 26 archived paraffin-embedded CRC tissues were also investigated by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR). Cell viability in response to the miR-96-5p inhibitor and mimic transfections was determined by an MTT assay. A Matrigel invasion assay was conducted to select the invasive subpopulation designated SW480-7, by using the parental cell line SW480. The effects of miR-96-5p mimic- or inhibitor-transfected SW480-7 cells on cell migration and invasion were evaluated using the Transwell and Matrigel assays, and the change in expression of the regulators of cytoskeleton mRNAs was identified by Cytoskeleton Regulators RT2-Profiler PCR array followed by validation with RT-qPCR. CRC tissues exhibited a significant increase in miR-96-5p expression, compared with their matched normal adjacent tissues, indicating an oncogenic role for miR-96-5p. The results demonstrated that the miR-96-5p inhibitor decreased the migration of SW480-7 cells, but had no effect on invasion. This may be due to the promotion of cell invasion by Matrigel, which counteracts the blockade of cell invasion by the miR-96-5p inhibitor. The miR-96-5p mimic enhanced SW480-7 cell migration and invasion, as expected. It was determined that there was a >2.5 fold increase in the expression of genes involved in cytoskeleton regulation, myosin light chain kinase 2, pleckstrin homology like domain family B member 2, cyclin A1, IQ motif containing GTPase activating protein 2, Brain-specific angiogenesisinhibitor 1-associated protein 2 and microtubule-actin crosslinking factor 1, in miR-96-5p inhibitor-transfected cells, indicating that they are negative regulators of cell migration. In conclusion, the miR-96-5p inhibitor blocked cell migration but not invasion, and the latter may be due to the counteraction of Matrigel, which has been demonstrated to stimulate cell invasion.
    Matched MeSH terms: Cell Movement
  19. Fulltext Incomplete cellular reprogramming of colorectal cancer cells elicits an epithelial/mesenchymal hybrid phenotype
    Hiew MSY, Cheng HP, Huang CJ, Chong KY, Cheong SK, Choo KB, et al.
    J Biomed Sci, 2018 Jul 19;25(1):57.
    PMID: 30025541 DOI: 10.1186/s12929-018-0461-1
    BACKGROUND: Induced pluripotency in cancer cells by ectopic expression of pluripotency-regulating factors may be used for disease modeling of cancers. MicroRNAs (miRNAs) are negative regulators of gene expression that play important role in reprogramming somatic cells. However, studies on the miRNA expression profile and the expression patterns of the mesenchymal-epithelial transition (MET)/epithelial-mesenchymal transition (EMT) genes in induced pluripotent cancer (iPC) cells are lacking.

    METHODS: iPC clones were generated from two colorectal cancer (CRC) cell lines by retroviral transduction of the Yamanaka factors. The iPC clones obtained were characterized by morphology, expression of pluripotency markers and the ability to undergo in vitro tri-lineage differentiation. Genome-wide miRNA profiles of the iPC cells were obtained by microarray analysis and bioinformatics interrogation. Gene expression was done by real-time RT-PCR and immuno-staining; MET/EMT protein levels were determined by western blot analysis.

    RESULTS: The CRC-iPC cells showed embryonic stem cell-like features and tri-lineage differentiation abilities. The spontaneously-differentiated post-iPC cells obtained were highly similar to the parental CRC cells. However, down-regulated pluripotency gene expression and failure to form teratoma indicated that the CRC-iPC cells had only attained partial pluripotency. The CRC-iPC cells shared similarities in the genome-wide miRNA expression profiles of both cancer and pluripotent embryonic stem cells. One hundred and two differentially-expressed miRNAs were identified in the CRC-iPC cells, which were predicted by bioinformatics analysis be closely involved in regulating cellular pluripotency and the expression of the MET/EMT genes, possibly via the phosphatidylinositol-3 kinases-protein kinase B (PI3K-Akt) and transforming growth factor beta (TGF-β) signaling pathways. Irregular and inconsistent expression patterns of the EMT vimentin and Snai1 and MET E-cadherin and occludin proteins were observed in the four CRC-iPC clones analyzed, which suggested an epithelial/mesenchymal hybrid phenotype in the partially reprogrammed CRC cells. MET/EMT gene expression was also generally reversed on re-differentiation, also suggesting epigenetic regulation.

    CONCLUSIONS: Our data support the elite model for cancer cell-reprogramming in which only a selected subset of cancer may be fully reprogrammed; partial cancer cell reprogramming may also elicit an epithelial-mesenchymal mixed phenotype, and highlight opportunities and challenges in cancer cell-reprogramming.

    Matched MeSH terms: Cell Movement/genetics
  20. MicroRNAs associated with tumour migration, invasion and angiogenic properties in A549 and SK-Lu1 human lung adenocarcinoma cells
    Ho CS, Yap SH, Phuah NH, In LL, Hasima N
    Lung Cancer, 2014 Feb;83(2):154-62.
    PMID: 24360396 DOI: 10.1016/j.lungcan.2013.11.024
    Dysregulation in miRNA expression contributes towards the initiation and progression of metastasis by regulating multiple target genes. In this study, variations in miRNA expression profiles were investigated between high and low invasive NSCLC cell lines followed by identification of miRNAs with targets governing NSCLC's metastatic potential.
    Matched MeSH terms: Cell Movement/genetics
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