8 results on '"Cheung, Annie N. Y."'
Search Results
2. MicroRNA-135a-induced formation of CD133+ subpopulation with cancer stem cell properties in cervical cancer.
- Author
-
Leung, Carmen O N, Deng, Wen, Ye, Tian-Min, Ngan, Hextan Y S, Tsao, Sai Wah, Cheung, Annie N Y, Ziru, Niu, Yuen, Dominic C K, Pang, Ronald T K, and Yeung, William S B
- Subjects
CANCER stem cells ,CERVICAL cancer ,EPITHELIAL cells ,CANCER cells - Abstract
Cancer stem cells (CSCs) play significant roles in tumor initiation. MicroRNA-135a (miR-135a) induced the formation of a CD133
+ subpopulation from a human papillomavirus-immortalized cervical epithelial cell line. Compared with the CD133− cells, the CD133+ cells expressed higher levels of miR-135a and OCT4, exhibited significantly higher tumorsphere forming capacity and the time required for tumorsphere formation was shortened in the second generation. Serum induction suppressed the expression of CD133, OCT4 and miR-135a, but increased expression of involucrin in the miR-135a-induced CD133+ cells. The miR-135a-induced CD133+ cells were tumorigenic in a limiting dilution approach in vivo. The cells expressed significantly higher level of active β-catenin and OCT4 than the CD133− counterpart. Wnt3a enhanced the expression of OCT4 and CD133 in cervical cancer cells but failed to enhance CD133 transcription in normal cervical cells. Wnt3a stimulation also increased tumorsphere size and self-renewal of miR-135a-induced CD133+ subpopulation. Wnt/β-catenin inhibition suppressed tumorsphere formation while Wnt3a partially nullified the inhibitory effect. Taken together, miR-135a induced the formation of a subpopulation of cells with CSC properties both in vitro and in vivo and the Wnt/β-catenin signaling pathway is essential to maintain its tumorigenicity. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
3. miR-135a leads to cervical cancer cell transformation through regulation of β-catenin via a SIAH1-dependent ubiquitin proteosomal pathway.
- Author
-
Leung CO, Deng W, Ye TM, Ngan HY, Tsao SW, Cheung AN, Pang RT, and Yeung WS
- Subjects
- Animals, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell virology, Cell Proliferation, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, Female, Gene Expression, HeLa Cells, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Transplantation, Oncogene Proteins, Viral metabolism, Papillomavirus Infections metabolism, Papillomavirus Infections pathology, Precancerous Conditions metabolism, Proteasome Endopeptidase Complex metabolism, Proteolysis, Ubiquitination, Up-Regulation, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms virology, beta Catenin genetics, Uterine Cervical Dysplasia pathology, Uterine Cervical Dysplasia virology, Carcinoma, Squamous Cell metabolism, MicroRNAs physiology, Nuclear Proteins metabolism, Ubiquitin-Protein Ligases metabolism, Uterine Cervical Neoplasms metabolism, beta Catenin metabolism, Uterine Cervical Dysplasia metabolism
- Abstract
Human papillomaviruses (HPVs) is the principal etiological agent of cervical cancer (CC). However, exposure to the high-risk type HPV alone is insufficient for tumor formation, and additional factors are required for the HPV-infected cells to become tumorigenic. Dysregulated microRNAs (miRNAs) expression is frequently observed in cancer but their roles in the formation of CC have not been fully revealed. In this study, we compared the expression of miR-135a in laser capture microdissected cervical specimens and confirmed overexpression of the miRNA in malignant cervical squamous cell carcinoma compared with precancerous lesions. Transient force-expression of miR-135a induced growth in low-density culture, anchorage-independent growth, proliferation and invasion of a HPV-16 E6/E7-immortalized cervical epithelial cell line, NC104-E6/E7. The observed effects were due to the inhibitory action of miR-135a on its direct target seven in absentia homolog 1 (SIAH1) leading to upregulation of β-catenin/T cell factor signaling. miR-135a force-expression enhanced the growth of HeLa- and NC104-E6/E7-derived tumor in vivo. The effect of miR-135a could be partially nullified by SIAH1 force-expression. More importantly, the expression of SIAH1 and β-catenin correlated with that of miR-135a in precancerous and cancerous lesions of cervical biopsies. By comparing the tumorigenic activities of miR-135a in E6/E7 positive/negative cell lines and in NC104-E6/E7 with or without E6/E7 knockdown, we demonstrated that HPV E6/E7 proteins are prerequisite for miR-135a as an oncomiR. Taken together, miR-135a/SIAH1/β-catenin signaling is important in the transformation and progression of cervical carcinoma., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2014
- Full Text
- View/download PDF
4. Downregulation of ASPP2 in choriocarcinoma contributes to increased migratory potential through Src signaling pathway activation.
- Author
-
Mak VC, Lee L, Siu MK, Wong OG, Lu X, Ngan HY, Wong ES, and Cheung AN
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Apoptosis, Apoptosis Regulatory Proteins metabolism, CSK Tyrosine-Protein Kinase, Cell Line, Tumor, Choriocarcinoma pathology, Down-Regulation, Female, Gene Expression Regulation, Neoplastic, Gestational Trophoblastic Disease pathology, Humans, Pregnancy, RNA Interference, Signal Transduction, src-Family Kinases metabolism, Apoptosis Regulatory Proteins genetics, Cell Movement genetics, Choriocarcinoma genetics, Gestational Trophoblastic Disease genetics, src-Family Kinases genetics
- Abstract
Gestational choriocarcinoma is a malignant tumor derived from placental trophoblast and the most aggressive member of gestational trophoblastic disease (GTD). Apoptosis-stimulating protein of p53-2 (ASPP2) is a member of ASPP family that transactivates p53 and thereby functions as a tumor suppressor. In this study, the expression profile of ASPP2 in choriocarcinoma was examined in comparison with normal placentas and hydatidiform moles, the latter being a type of GTD that carries malignant potential. Downregulation of ASPP2 messenger RNA and protein was demonstrated in choriocarcinoma by quantitative PCR and immunohistochemistry. ASPP2-transfected choriocarcinoma cells (JEG-3 and JAR) showed an increase in apoptosis and a decrease in cell migration as detected by TdT-mediated dUTP nick end labeling and wound healing assays, respectively, illustrating the complex action of ASPP2 on cell functions other than programmed cell death. Activated Src is known to be important in tumor progression. Transfection of ASPP2 but not ASPP1, another tumor-suppressive ASPP, was found to be related to subsequent decreased Src-pY416 phosphorylation, suggesting an inactivating effect of ASPP2 on Src. Moreover, this ASPP2-mediated inactivation of Src could be abolished by RNA interference with C-terminal Src kinase (Csk), a kinase that can inhibit Src activation. Our findings suggested that the ability of ASPP2 to attenuate Src activation was specific to ASPP2 in a Csk-dependent manner. Taken together, we demonstrated a loss of tumor-suppressive ASPP2 in choriocarcinoma with effects on cell migration and apoptosis. We also unveiled a possible mechanistic link between ASPP2 and Csk/Src signaling pathway, implicating the multiple cellular functions of ASPP2.
- Published
- 2013
- Full Text
- View/download PDF
5. Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma.
- Author
-
Zhang HJ, Siu MK, Yeung MC, Jiang LL, Mak VC, Ngan HY, Wong OG, Zhang HQ, and Cheung AN
- Subjects
- 1-Phosphatidylinositol 4-Kinase pharmacology, Apoptosis, Blotting, Western, Cell Adhesion, Cell Line, Tumor, Choriocarcinoma genetics, Choriocarcinoma metabolism, Chorionic Gonadotropin pharmacology, Female, Gestational Trophoblastic Disease, Humans, Immunoenzyme Techniques, Matrix Metalloproteinase 14 genetics, Matrix Metalloproteinase 14 metabolism, Pregnancy, RNA, Messenger genetics, RNA, Small Interfering genetics, Reverse Transcriptase Polymerase Chain Reaction, Trophoblastic Neoplasms genetics, Trophoblastic Neoplasms metabolism, Trophoblastic Neoplasms pathology, Uterine Neoplasms genetics, Uterine Neoplasms metabolism, p21-Activated Kinases antagonists & inhibitors, p21-Activated Kinases genetics, Cell Movement, Cell Proliferation, Choriocarcinoma pathology, Uterine Neoplasms pathology, p21-Activated Kinases metabolism
- Abstract
Gestational trophoblastic disease (GTD) includes frankly malignant choriocarcinoma (CCA) and placental site trophoblastic tumor and potentially malignant hydatidiform mole. p21-Activated kinase (PAK) 4 promotes cell motility. This study investigated the role of PAK4 in the pathogenesis of GTD. PAK4 messenger RNA and protein expressions in clinical samples and cell lines of normal placentas and GTD were determined by quantitative real-time polymerase chain reaction and western blot, respectively. The effects of human chorionic gonadotropin (hCG) and phosphoinositide 3 kinase (PI3K) on the expression and activation of PAK4 were investigated by treating CCA JEG3 and JAR cells with anti-hCG antibody and PI3K inhibitor, respectively. The effects of PAK4 on CCA cell proliferation, migration and invasion were assessed by corresponding functional assays. We demonstrated overexpression of PAK4 in GTD and CCA cell lines at both RNA and protein level. hCG is one of the upstream regulators of PAK4 expression, whereas activation of PAK4 is PI3K/PKB dependent in JEG3 and JAR cells. Significant correlation was found between PAK4 expression and proliferation index minichromosome maintenance complex component 7 (P = 0.007). In JEG3 and JAR cells, stably transfected PAK4 increased proliferation, migration and invasion, whereas small interfering RNA knockdown of PAK4 decreased proliferation, migration and invasion along with downregulated CDK6 and membrane-type 1 matrix metalloproteinase (MT1-MMP) and upregulated p16. We further found PAK4-mediated transcription of MT1-MMP in CCA cells by luciferase reporter assay. Our results demonstrated for the first time that overexpressed PAK4 was involved in the pathogenesis of GTD, promoting proliferation and enhancing cell migration and invasion in CCA cells.
- Published
- 2011
- Full Text
- View/download PDF
6. Tumor suppressor effect of follistatin-like 1 in ovarian and endometrial carcinogenesis: a differential expression and functional analysis.
- Author
-
Chan QK, Ngan HY, Ip PP, Liu VW, Xue WC, and Cheung AN
- Subjects
- Apoptosis, Blotting, Western, Cell Proliferation, Down-Regulation, Endometrial Neoplasms pathology, Female, Flow Cytometry, Follistatin-Related Proteins genetics, Humans, In Situ Nick-End Labeling, Neoplasm Invasiveness, Neoplasm Metastasis, Ovarian Neoplasms pathology, Reverse Transcriptase Polymerase Chain Reaction, Endometrial Neoplasms physiopathology, Follistatin-Related Proteins physiology, Genes, Tumor Suppressor, Ovarian Neoplasms physiopathology
- Abstract
Endometrial and ovarian cancers are the most common and the most lethal gynecologic malignancies worldwide, respectively. By performing differential expression analysis using annealing control primer-based reverse transcription (RT)-polymerase chain reaction (PCR) on pooled complementary DNA (cDNA) from 45 endometrial and 36 ovarian cancers and their non-tumor samples, reduced expression of the follistatin-like 1 (FSTL1) was identified. Downregulation of FSTL1 was further confirmed on individual samples and cell lines by quantitative real-time RT-PCR and western blotting. For in vitro functional study, full-length cDNA of FSTL1 was cloned and transiently transfected into the ovarian cancer cell line Ovca420 and endometrial cancer cell line AN3CA. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count demonstrated significantly slower proliferation rate. By terminal uridine deoxynucleotidyl transferase dUTP nick end labeling and flow cytometric analysis, higher apoptotic activity and a remarkable increase in sub-G(1) cell population were observed in transfected cells, suggesting that FSTL1 induced apoptosis in cancer cells. Subsequent messenger RNA and protein expression analysis on downstream apoptotic molecules revealed upregulation and/or activation of FAS, FASLG, TRADD, Caspase-3, Caspase-7 and PARP by FSTL1 transfection, suggesting that FSTL1-induced apoptosis may be initiated mainly by FAS/FASLG death receptor-ligand binding. Cell migration and invasion assays demonstrated a remarkably lower cell migration and invasion capability in FSTL1-transfected cells in relation to downregulation of matrix metallopeptidase-2. Our findings suggested that a tumor suppressor role of FSTL1 may be important in ovarian and endometrial carcinogenesis.
- Published
- 2009
- Full Text
- View/download PDF
7. Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation.
- Author
-
Liao X, Siu MK, Au CW, Wong ES, Chan HY, Ip PP, Ngan HY, and Cheung AN
- Subjects
- Cell Line, Tumor, Female, Humans, Immunohistochemistry, Ovarian Neoplasms metabolism, Patched Receptors, Prognosis, Receptors, Cell Surface metabolism, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors metabolism, Zinc Finger Protein GLI1, Cell Differentiation, Hedgehog Proteins metabolism, Neoplasm Invasiveness, Ovarian Neoplasms pathology, Signal Transduction
- Abstract
Aberrant activation of hedgehog (HH) pathway has been implicated in the development of human malignancies. This study aimed at investigating the role of HH molecules in human ovarian carcinogenesis. The expression profiles of HH molecules were examined in ovarian tumor samples and ovarian cancer cell lines and the in vitro effects of HH molecules on cell proliferation, apoptosis, migration, invasion and cell differentiation as well as related downstream target genes were assessed. Overexpression of Patched and Gli1 protein in ovarian cancers correlated with poor survival of the patients (P = 0.008; P = 0.004). Significantly elevated expression of Sonic hedgehog messenger RNA was observed in ovarian cancers compared with normal tissues and benign ovarian tumors and such differential expression was specific to histological types (P < 0.05). Ectopic Gli1 overexpression in ovarian cancer cells conferred increased cell proliferation, cell mobility, invasiveness and change in differentiation in association with increased expression of E-cadherin, vimentin, Bcl-2, caspases as well as beta1 integrin, membrane type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF). Treatment with 3-keto-N-(aminoethyl-aminocaproyl-dihydrocinnamoyl)-cyclopamine induced cancer cell apoptosis, suppressed cell growth, mobility and invasiveness and induced cancer cell dedifferentiation with decreased expression of E-cadherin, cytokeratin 7, Snail, calretinin, vimentin, Bcl-2, caspases, beta1 integrin, MT1-MMP and VEGF. Our data suggested that abnormal HH signaling activation plays important roles in the development and progression of ovarian cancers. Gli1 expression is an independent prognostic marker. Inhibition of the HH pathway molecules might be a valid therapeutic strategy for ovarian cancers.
- Published
- 2009
- Full Text
- View/download PDF
8. Follicle stimulating hormone can act on receptors of other growth hormone.
- Author
-
Cheung AN, Siu MK, Au CW, Chan HY, and Wong E
- Subjects
- Cell Line, Tumor, Female, Follicle Stimulating Hormone pharmacology, Humans, Ovarian Neoplasms, Ovulation drug effects, Follicle Stimulating Hormone physiology, Receptors, FSH physiology, Receptors, Somatotropin physiology
- Published
- 2007
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.