28 results on '"YANLING ZHANG"'
Search Results
2. TGF-β1 in Seminal Plasma Promotes Endometrial Mesenchymal Stem Cell Growth via p42/44 and Akt Pathway in Patients With or Without Endometriosis
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Jing Li, Yongdong Dai, Chao Li, Yanling Zhang, Haiyan Zhu, Xiaoying Jin, Xiang Lin, Jianmin Chen, Lijuan Zhao, and Songying Zhang
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Adult ,Cell Cycle ,Endometriosis ,Obstetrics and Gynecology ,Mesenchymal Stem Cells ,Transforming Growth Factor beta1 ,Endometrium ,Mice ,Semen ,Animals ,Cytokines ,Humans ,Female ,Mitogen-Activated Protein Kinases ,Proto-Oncogene Proteins c-akt ,Biomarkers ,Cells, Cultured ,Cell Proliferation ,Signal Transduction - Abstract
The cause of endometriosis, which is characterized by the existence of functional endometrial tissue outside the uterine cavity, is poorly understood. Seminal plasma (SP) is rich in multiple cytokines that may promote endometrial tissue survival. Here, we evaluated the effect of SP on growth of endometrial mesenchymal stem cells (MSCs) from women with endometriosis (E-MSCs) and women without endometriosis (NE-MSCs). Proliferation, cell foci formation, cell cycle progression, and growth marker expression of E- and NE-MSCs were promoted by SP. These effects may be mediated through activation of transforming growth factor beta 1 (TGF-β1), Akt, and p42/44 signaling, which enhances CDK2 and CDK6 expression and accelerates cell cycle progression. Xenografts exposed to SP exhibited a three-fold increase in volume and four-fold increase in weight after 14 days. Our findings demonstrate that TGF-β1 in SP may promote endometrial tissue survival which will allow us to understand the pathogenesis and develop novel approaches for prevention and therapies of endometriosis.
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- 2022
3. Thyroid-stimulating hormone decreases the risk of osteoporosis by regulating osteoblast proliferation and differentiation
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Jin Xu, Wenwen Zhang, Xiujuan Zhang, Chunxiao Yu, Zhikun Huan, Yanling Zhang, Mengqi Zhang, Yan Wang, and Tuo Deng
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0301 basic medicine ,Male ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Thyrotropin ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Bone remodeling ,0302 clinical medicine ,Bone Density ,Risk Factors ,Cells, Cultured ,Bone mineral ,TSH ,Osteoblast ,Cell Differentiation ,General Medicine ,Middle Aged ,RUNX2 ,medicine.anatomical_structure ,Triiodothyronine ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,Adult ,musculoskeletal diseases ,medicine.medical_specialty ,China ,endocrine system ,030209 endocrinology & metabolism ,Bone morphogenetic protein ,03 medical and health sciences ,Thyroid-stimulating hormone ,BMD ,Internal medicine ,medicine ,Animals ,Humans ,Cell Proliferation ,Osteoblasts ,lcsh:RC648-665 ,business.industry ,medicine.disease ,Rats ,Thyroxine ,030104 developmental biology ,Endocrinology ,Cross-Sectional Studies ,Animals, Newborn ,business ,Hormone - Abstract
Background As the incidence of secretory osteoporosis has increased, bone loss, osteoporosis and their relationships with thyroid-stimulating hormone (TSH) have received increased attention. In this study, the role of TSH in bone metabolism and its possible underlying mechanisms were investigated. Methods We analyzed the serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSH and the bone mineral density (BMD) levels of 114 men with normal thyroid function. In addition, osteoblasts from rat calvarial samples were treated with different doses of TSH for different lengths of time. The related gene and protein expression levels were investigated. Results A comparison of the BMD between the high-level and low-level serum TSH groups showed that the TSH serum concentration was positively correlated with BMD. TSH at concentrations of 10 mU/mL and 100 mU/mL significantly increased the mRNA levels of ALP, COI1 and Runx2 compared with those of the control (P P Conclusions The circulating concentrations of TSH and BMD were positively correlated with normal thyroid function in males. TSH promoted osteoblast proliferation and differentiation in rat primary osteoblasts.
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- 2021
4. circRNA LDLRAD3 Enhances the Malignant Behaviors of NSCLC Cells via the miR-20a-5p-SLC7A5 Axis Activating the mTORC1 Signaling Pathway
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Yu Li, Guangle Qin, Jinyun Du, Peng Yue, Yanling Zhang, and Na Hou
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Medicine (General) ,Lung Neoplasms ,Article Subject ,Biomedical Engineering ,Health Informatics ,RNA, Circular ,Mechanistic Target of Rapamycin Complex 1 ,Large Neutral Amino Acid-Transporter 1 ,MicroRNAs ,R5-920 ,Carcinoma, Non-Small-Cell Lung ,Medical technology ,Humans ,Surgery ,R855-855.5 ,Biotechnology ,Research Article ,Cell Proliferation ,Signal Transduction - Abstract
Circular RNA LDLRAD3 behaved as an oncogene in several malignancies, but its effects in NSCLC and the involvement of downstream molecules and activation of signaling pathways had not been fully reported. We planned to explore how LDLRAD3 facilitated the malignancy of NSCLC. QRT-PCR was performed to evaluate the expression levels of LDLRAD3, miR-20a-5p, and SLC7A5 in NSCLC tissues and cells. si-LDLRAD3 was transfected to A549 and H1299 cells to knock down intrinsic LDLRAD3 to determine its oncogenic roles. CCK-8 assay and transwell assay were executed to assess cell proliferative, migrative, and invasive abilities. Dual-luciferase reporter (DLR) assay was manipulated to verify the ENCORI-predicted relationships between LDLRAD3 and miR-20a-5p and between miR-20a-5p and SLC7A5. Western blot, immunofluorescent assay, and immunohistochemistry were applied to explore the expression levels of SLC7A5, and the levels of mTORC1 pathway-related proteins were evaluated using western blot. Rescue experiments were conducted by transfecting si-LDLRAD3, miR-20a-5p inhibitor, and si-SLC7A5 to explore the influence of the LDLRAD3-miR-20a-5p-SLC7A5 axis on the malignant behaviors of NSCLC cells. The expression levels of LDLRAD3 and SLC7A5 were boosted, whereas miR-20a-5p was impeded in NSCLC tissues and cell lines. Knockdown of LDLRAD3 weakened the proliferation, migration, and invasion of A549 and H1299 cells. LDLRAD3 was verified to sponge miR-20a-5p and miR-20a-5p targeted SLC7A5. LDLRAD3 activated the mTORC1 singling pathway via the miR-20a-5p-SLC7A5 axis to strengthen the malignant properties of A549 and H1299 cells. We concluded that LDLRAD3 exerted oncogenic effects via the miR-20a-5p-SLC7A5 axis to activate the mTORC1 signaling pathway in NSCLC. Our findings enlightened that LDLRAD3 could become a potential therapeutic target in the treatment and management of NSCLC.
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- 2022
5. Circ_0075804 promotes the malignant behaviors of retinoblastoma cells by binding to miR-138-5p to induce PEG10 expression
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Xiaoyan Dou, Yanling Zhang, Qinghui Kong, Yuying Li, and Xing Zhou
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Untranslated region ,Gene knockdown ,medicine.diagnostic_test ,Retinoblastoma ,Cell growth ,business.industry ,Retinal Neoplasms ,RNA-Binding Proteins ,Cell migration ,RNA, Circular ,medicine.disease ,Molecular biology ,Flow cytometry ,DNA-Binding Proteins ,Ophthalmology ,MicroRNAs ,Gentamicin protection assay ,Cell culture ,medicine ,Humans ,business ,Apoptosis Regulatory Proteins ,Cell Proliferation - Abstract
It has been gradually recognized that circular RNAs (circRNAs) are important modulators in multiple malignancies. Here, we analyzed the function of circ_0075804 and explored its associated mechanism in regulating retinoblastoma (RB) progression. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were utilized to measure RNA and protein expression, respectively. Cell proliferation was analyzed by Cell counting kit-8 (CCK8) assay and 5-Ethynyl-2’-deoxyuridine (EdU) assay. Cell apoptosis was assessed by flow cytometry. Cell migration and invasion abilities were analyzed by wound healing assay and transwell invasion assay. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to verify intermolecular target relations. Xenograft tumor model was used to analyze the role of circ_0075804 in tumor growth in vivo. Circ_0075804 expression was markedly up-regulated in RB tissues and cell lines. Circ_0075804 knockdown restrained the proliferation, migration and invasion whereas promoted the apoptosis of RB cells. Circ_0075804 acted as a molecular sponge for microRNA-138-5p (miR-138-5p), and circ_0075804 silencing-induced effects were partly reversed by miR-138-5p knockdown in RB cells. MiR-138-5p interacted with the 3’ untranslated region (3’UTR) of paternally expressed 10 (PEG10). Circ_0075804 positively regulated PEG10 level by sponging miR-138-5p in RB cells. PEG10 overexpression largely overturned miR-138-5p overexpression-mediated effects in RB cells. Circ_0075804 knockdown blocked xenograft tumor growth in vivo. Circ_0075804 promoted RB progression via miR-138-5p-dependent regulation of PEG10, which provided new insight in RB therapy.
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- 2021
6. A collagen scaffold loaded with human umbilical cord-derived mesenchymal stem cells facilitates endometrial regeneration and restores fertility
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Yibin Pan, Xiaowen Zheng, Songying Zhang, Lie Ma, Yanling Zhang, Changyou Gao, Libing Shi, Xiaona Lin, and Liaobing Xin
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Vascular Endothelial Growth Factor A ,Human Embryonic Stem Cells ,0206 medical engineering ,Becaplermin ,Biomedical Engineering ,Uterus ,Estrogen receptor ,02 engineering and technology ,Mesenchymal Stem Cell Transplantation ,Endometrium ,Biochemistry ,Epithelium ,Umbilical Cord ,Rats, Sprague-Dawley ,Transforming Growth Factor beta1 ,Biomaterials ,Andrology ,Paracrine signalling ,Paracrine Communication ,Animals ,Humans ,Regeneration ,Medicine ,Molecular Biology ,Cell Proliferation ,Endometrial Stromal Cell ,Tissue Scaffolds ,business.industry ,Regeneration (biology) ,Mesenchymal stem cell ,Estrogen Receptor alpha ,Mesenchymal Stem Cells ,General Medicine ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Transplantation ,Fertility ,Ki-67 Antigen ,medicine.anatomical_structure ,Keratins ,Cattle ,Female ,Collagen ,Receptors, Progesterone ,0210 nano-technology ,business ,Biotechnology - Abstract
In women of reproductive age, severe injuries to the endometrium are often accompanied by endometrial scar formation or intrauterine adhesions (IUAs), which can result in infertility or miscarriage. Although many approaches have been used to treat severe IUAs, high recurrence rates and endometrial thinning have limited therapeutic efficiency. In this study, a collagen scaffold (CS) loaded with human umbilical cord-derived mesenchymal stem cells (UC-MSCs) was fabricated and applied for endometrial regeneration. The CS/UC-MSCs promoted human endometrial stromal cell proliferation and inhibited apoptosis in vitro through paracrine effects. In a model of endometrial damage, transplantation with the CS/UC-MSCs maintained normal luminal structure, promoted endometrial regeneration and collagen remodeling, induced intrinsic endometrial cell proliferation and epithelium recovery, and enhanced the expression of estrogen receptor α and progesterone receptor. An improved ability of the regenerated endometrium to receive embryos was confirmed. Together, our results indicate that the CS/UC-MSCs promoted endometrial structural reconstruction and functional recovery. Topical administration of the CS/UC-MSCs after trans-cervical resection of adhesions might prevent re-adhesion, promote endometrium regeneration and improve pregnancy outcomes for patients with severe IUAs. STATEMENT OF SIGNIFICANCE: Intrauterine adhesions due to severe endometrium injuries happen frequently in clinic and become one of the crucial reasons for women's infertility or miscarriage. Therefore, how to regenerate the damaged endometrium is a big challenge. In this study, a collagen scaffold (CS) loaded with human umbilical cord-derived mesenchymal stem cells (UC-MSCs) was fabricated and applied for endometrium regeneration. Herein, UC-MSCs, known for low immunogenicity and high proliferative potential, exhibit promising potential for endometrium regeneration; and collagen scaffolds provide suitable physical support. It was proved that transplantation with CS/UC-MSCs promoted endometrial regeneration and fertility restoration. It suggested that topical administration of CS/UC-MSCs in uterus could be a promising strategy for patients suffering severe intrauterine adhesion and infertility.
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- 2019
7. T cell immunoglobulin and mucin domain protein 3 inhibits glycolysis in RAW 264.7 macrophages through Hexokinase 2
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Yiqiong Liu, Shuaijie Dou, Beifen Shen, Ge Li, Chunmei Hou, Renxi Wang, Yanling Zhang, Zhiding Wang, Jiacheng Zhang, and Gencheng Han
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Male ,T cell ,T-Lymphocytes ,Immunology ,Interleukin-1beta ,Apoptosis ,Proinflammatory cytokine ,Cell Line ,Mice ,Hexokinase ,medicine ,Macrophage ,Animals ,Humans ,Glycolysis ,Hepatitis A Virus Cellular Receptor 2 ,Cell Proliferation ,Inflammation ,Innate immune system ,Chemistry ,Tumor Necrosis Factor-alpha ,Macrophages ,Interleukin ,General Medicine ,Immune checkpoint ,Immunity, Innate ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,HEK293 Cells ,RAW 264.7 Cells ,Cytokines ,Tumor necrosis factor alpha ,Signal Transduction - Abstract
T cell immunoglobulin and mucin domain-3 (Tim-3), an immune checkpoint molecule, plays critical roles in maintaining innate immune homeostasis; however, the mechanisms underlying these roles remain to be determined. Here, we determined that Tim-3 controls glycolysis in macrophages and thus contributes to phenotype shifting. Tim-3 signal blockade significantly increases lactate production by macrophages, but does not influence cell proliferation or apoptosis. Tim-3 attenuates glucose uptake by inhibiting hexokinase 2 (HK2) expression in macrophages. Tim-3-mediated inhibition of macrophage glycolysis and the expression of proinflammatory cytokines, tumour necrosis factor (TNF)-α and interleukin (IL)-1β are reversed by HK2 silencing. Finally, we demonstrated that Tim-3 inhibits HK2 expression via the STAT1 pathway. We have thus discovered a new way by which Tim-3 modulates macrophage function.
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- 2020
8. Rosmarinic Acid as a Candidate in a Phenotypic Profiling Cardio-/Cytotoxicity Cell Model Induced by Doxorubicin
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Jing Li, Qiao Zhang, Yanling Zhang, Yanjiang Qiao, and Sha Peng
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rosmarinic acid ,Cell ,Induced Pluripotent Stem Cells ,Pharmaceutical Science ,phenotypic profiling ,Apoptosis ,030204 cardiovascular system & hematology ,Pharmacology ,Cell morphology ,Depsides ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,0302 clinical medicine ,lcsh:Organic chemistry ,Neoplasms ,Drug Discovery ,medicine ,Humans ,Doxorubicin ,Myocytes, Cardiac ,Physical and Theoretical Chemistry ,Cytotoxicity ,Cells, Cultured ,030304 developmental biology ,Cell Proliferation ,chemistry.chemical_classification ,0303 health sciences ,Reactive oxygen species ,Cardiotoxicity ,Antibiotics, Antineoplastic ,GATA4 ,hiPSC-CMs ,Organic Chemistry ,Cell Differentiation ,medicine.anatomical_structure ,chemistry ,morphological pattern recognition ,Chemistry (miscellaneous) ,Cinnamates ,Molecular Medicine ,medicine.drug - Abstract
Advances in cancer treatment have led to significant improvements in long-term survival in many types of cancer, but heart dysfunction and heart failure, associated with cancer treatment, have also increased. Anthracyclines are the main cause of this type of cardiotoxicity. In this study, we describe a combined experimental and cell morphology analysis approach for the high-throughput measurement and analysis of a cardiomyocyte cell profile, using partial least square linear discriminant analysis (PLS-LDA) as the pattern recognition algorithm. When screening a small-scale natural compound library, rosmarinic acid (RosA), as a candidate drug, showed the same cardioprotective effect as the positive control. We investigated the protective mechanism of RosA on a human cardiomyocyte cell line (AC16) and human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). We showed that RosA pretreatment suppressed doxorubicin (Dox)-induced cell apoptosis and decreased the activity of caspase-9. RosA promotes the expression of Heme oxygenase-1 (HO-1) and reduces the production of reactive oxygen species (Ros), which is induced by Dox. Meanwhile, it can also promote the expression of cardiac-development-related protein, including histone deacetylase 1 (HDAC1), GATA binding protein 4 (GATA4) and troponin I3, cardiac type (CTnI). Collectively, our data support the notion that RosA is a protective agent in hiPSC-CMs and has the potential for therapeutic use in the treatment of cancer therapy-related cardiac dysfunction and heart failure.
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- 2020
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9. AAV-Mediated angiotensin 1-7 overexpression inhibits tumor growth of lung cancer in vitro and in vivo
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Na Bai, Wang Shengyao, Hongwei Li, Nana Pei, Andrew Li, Colin Sumners, Renhe Yan, Yanling Zhang, Baihong Chen, Sansan Chen, Xinglu Chen, Hongyan Du, Jinlong Li, and Yingying Mao
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0301 basic medicine ,Gerontology ,Vascular Endothelial Growth Factor A ,Lung Neoplasms ,Cell Cycle Proteins ,Mice ,0302 clinical medicine ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,Lung ,Mice, Inbred BALB C ,Neovascularization, Pathologic ,Nuclear Proteins ,Dependovirus ,Immunohistochemistry ,Oncology ,030220 oncology & carcinogenesis ,Molecular mechanism ,Female ,adeno-associated viral vector ,Research Paper ,DNA Replication ,Epithelial-Mesenchymal Transition ,proliferation ,Genetic Vectors ,Down-Regulation ,Mice, Nude ,Viral vector ,03 medical and health sciences ,Ang-(1-7) ,In vivo ,Multienzyme Complexes ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Tumor growth ,Lung cancer ,Cell Proliferation ,Angiotensin 1 ,DNA synthesis ,business.industry ,medicine.disease ,Xenograft Model Antitumor Assays ,In vitro ,Peptide Fragments ,lung cancer ,030104 developmental biology ,Lung cancer cell ,Proteolysis ,Cancer research ,Angiotensin I ,business - Abstract
// Xinglu Chen 1, * , Sansan Chen 2, * , Nana Pei 3, * , Yingying Mao 1 , Shengyao Wang 1 , Renhe Yan 1 , Na Bai 4 , Andrew Li 5 , Yanling Zhang 1 , Hongyan Du 1 , Baihong Chen 1 , Colin Sumners 6 , Jinlong Li 1 , Hongwei Li 1 1 School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China 2 Department of Urology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China 3 Department of Clinical Pathology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China 4 Deparement of Nuclear Medicine, People’s Hospital of Yuxi City, Yuxi, Yunnan, China 5 Department of Biomedical Engineering, The Johns University School of Medicine, Baltimore, USA 6 Departments of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA * These authors contributed equally to this work Correspondence to: Hongwei Li, email: hongwei1@yahoo.com Jinglong Li, email: lijinlong75@126.com Keywords: Ang-(1-7), lung cancer, adeno-associated viral vector, DNA synthesis, proliferation Received: October 07, 2016 Accepted: November 11, 2016 Published: November 16, 2016 ABSTRACT Ang-(1-7) inhibits lung cancer cell growth both in vitro and in vivo . However, the molecular mechanism of action is unclear and also the rapid degradation of Ang-(1-7) in vivo limits its clinical application. Here, we have demonstrated that Ang- (1-7) inhibits lung cancer cell growth by interrupting pre-replicative complex assembly and restrains epithelial-mesenchymal transition via Cdc6 inhibition. Furthermore, we constructed a mutant adeno-associated viral vector AAV8 (Y733F) that produced stable and high efficient Ang-(1-7) expression in a xenograft tumor model. The results show that AAV8-mediated Ang-(1-7) over-expression can remarkably suppress tumor growth in vivo by down-regulating Cdc6 and anti-angiogenesis. Ang-(1-7) over-expression via the AAV8 method may be a promising strategy for lung cancer treatment.
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- 2016
10. NKAIN2 functions as a novel tumor suppressor in prostate cancer
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Daniel M. Berney, Jacek Marzec, Attila T. Lorincz, Fei Luo, Elzbieta Stankiewicz, Guoping Ren, Nataša Vasiljević, Yong Jiang, Shan-Chao Zhao, Claude Chelala, Lara K. Boyd, Yongwei Yu, Yanling Zhang, Yong-Jie Lu, Jia Xu, Ninghan Feng, Bo-wei Zhou, and Xueying Mao
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0301 basic medicine ,Gerontology ,Oncology ,Male ,DNA Mutational Analysis ,Apoptosis ,Haploidy ,Prostate cancer ,0302 clinical medicine ,Prostate ,Cell Movement ,Genes, Tumor Suppressor ,RNA, Small Interfering ,Promoter Regions, Genetic ,In Situ Hybridization, Fluorescence ,education.field_of_study ,chromosomal deletion and truncation ,High-Throughput Nucleotide Sequencing ,Genomics ,prostate cancer ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Research Paper ,medicine.medical_specialty ,population difference ,Tumor suppressor gene ,tumor suppressor ,Population ,03 medical and health sciences ,Internal medicine ,Cell Line, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,education ,Preventive healthcare ,Cell Proliferation ,Cancer prevention ,NKAIN2 ,business.industry ,Cancer ,Membrane Proteins ,Prostatic Neoplasms ,DNA Methylation ,medicine.disease ,030104 developmental biology ,Cancer cell ,Mutation ,business ,Gene Deletion - Abstract
// Xueying Mao 1, * , Fei Luo 2, 3, * , Lara K. Boyd 1, * , Bowei Zhou 2, 3 , Yanling Zhang 4, 5 , Elzbieta Stankiewicz 1 , Jacek Marzec 1 , Natasa Vasiljevic 6 , Yongwei Yu 7 , Ninghan Feng 8 , Jia Xu 3 , Attila Lorincz 6 , Yong Jiang 3 , Claude Chelala 1 , Guoping Ren 4 , Daniel M Berney 1 , Shan-Chao Zhao 2 , Yong-Jie Lu 1 1 Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK 2 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China 3 Key Laboratory of Proteomics of Guangdong Province and Key Laboratory of Transcriptomics and Proteomics of Human Diseases Supported by The Ministry of Education of China, Southern Medical University, Guangzhou, 510515, China 4 Department of Pathology, The First Affiliated Hospital, Zhejiang University Medical College, Hangzhou, 310009, China 5 Department of Gynecology and Obstetrics, Sir Run Run Shaw Hospital, Zhejiang University Medical College, Hangzhou, 310009, China 6 Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK 7 Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China 8 Department of Urology, Wuxi Second People’s Hospital, Nanjing Medical University, Wuxi, 214002, China * These authors contributed equally to this work Correspondence to: Shan-Chao Zhao, email: zhaoshanchao@263.net Yong-Jie Lu, email: y.j.lu@qmul.ac.uk Keywords: NKAIN2, tumor suppressor, prostate cancer, chromosomal deletion and truncation, population difference Received: December 16, 2015 Accepted: August 22, 2016 Published: August 30, 2016 ABSTRACT Recurrent chromosome breakpoints at 6q22.31, leading to truncation and potential loss-of-function of the NKAIN2 gene, in Chinese prostate cancer patients were previously identified. In this study we investigated genomic, methylation and expression changes of NKAIN2 in a large number of prostate cancer samples and determined its functional role in prostate cancer cells. Fluorescence in situ hybridization analysis confirmed that NKAIN2 truncation is specific to Chinese while deletion of the gene is frequent in both Chinese and UK prostate cancers. Significantly reduced expression of NKAIN2 was also detected at both RNA and protein levels. Somatic mutations of NKAIN2 in prostate cancer samples exist but at very low frequency, suggesting that it is a putative tumor suppressor gene (TSG) with haploid insufficiency. Our functional studies showed that overexpression of NKAIN2 in prostate cancer cells inhibits cellular growth by promoting cell apoptosis, and decreasing cell migration and invasion. Conversely, knockdown of NKAIN2 promotes prostate cancer cell growth by inhibiting cell apoptosis, and increasing cell migration and invasion. These data imply that NKAIN2 is a novel TSG whose activity is commonly reduced in prostate cancer. It may restrain the disease development and progression by inducing apoptosis and suppressing cancer cell growth, migration and invasion. This study provides new insights into prostate carcinogenesis and opportunities for development of novel therapies for prostate cancer.
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- 2016
11. Angiotensin-(1-7) Decreases Cell Growth and Angiogenesis of Human Nasopharyngeal Carcinoma Xenografts
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Haifa Zheng, Andrew Li, Michael J. Katovich, Wenjin Wei, Hongwei Li, Hongyan Du, Colin Sumners, Yanfei Qi, Yanling Zhang, Nana Pei, Jinlong Li, Yi Zhang, Renqiang Wan, Xinglu Chen, and Baihong Chen
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Vascular Endothelial Growth Factor A ,0301 basic medicine ,Cancer Research ,MAP Kinase Signaling System ,medicine.drug_class ,Angiogenesis ,Angiogenesis Inhibitors ,Proto-Oncogene Mas ,Neovascularization ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Receptor ,Cell Proliferation ,Nasopharyngeal Carcinoma ,Neovascularization, Pathologic ,Chemistry ,Cell growth ,Carcinoma ,Membrane Proteins ,Nasopharyngeal Neoplasms ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Receptor antagonist ,Xenograft Model Antitumor Assays ,Peptide Fragments ,Tumor Burden ,Disease Models, Animal ,Receptors, Vascular Endothelial Growth Factor ,030104 developmental biology ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Adenocarcinoma ,Female ,Angiotensin I ,medicine.symptom - Abstract
Angiotensin-(1-7) [Ang-(1-7)] is an endogenous, heptapeptide hormone acting through the Mas receptor (MasR), with antiproliferative and antiangiogenic properties. Recent studies have shown that Ang-(1-7) has an antiproliferative action on lung adenocarcinoma cells and prostate cancer cells. In this study, we report that MasR levels were significantly upregulated in nasopharyngeal carcinoma (NPC) specimens and NPC cell lines. Viral vector–mediated expression of Ang-(1-7) dramatically suppressed NPC cell proliferation and migration in vitro. These effects were completely blocked by the specific Ang-(1-7) receptor antagonist A-779, suggesting that they are mediated by the Ang-(1-7) receptor Mas. In this study, Ang-(1-7) not only caused a significant reduction in the growth of human nasopharyngeal xenografts, but also markedly decreased vessel density, suggesting that the heptapeptide inhibits angiogenesis to reduce tumor size. Mechanistic investigations revealed that Ang-(1-7) inhibited the expression of the proangiogenic factors VEGF and PlGF. Taken together, the data suggest that upregulation of MasR could be used as a diagnostic marker of NPC and Ang-(1-7) may be a novel therapeutic agent for nasopharyngeal cancer therapy because it exerts significant antiangiogenic activity. Mol Cancer Ther; 15(1); 37–47. ©2015 AACR.
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- 2016
12. Activation of the Hippo/TAZ pathway is required for menstrual stem cells to suppress myofibroblast and inhibit transforming growth factor β signaling in human endometrial stromal cells
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Jing Li, Haiyan Zhu, Yibin Pan, Yanling Zhang, Songying Zhang, and Yinshen Jiang
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Stromal cell ,Biology ,Protein Serine-Threonine Kinases ,03 medical and health sciences ,Endometrium ,0302 clinical medicine ,Transforming Growth Factor beta ,Humans ,Hippo Signaling Pathway ,Myofibroblasts ,Cells, Cultured ,Endometrial Stromal Cell ,Cell Proliferation ,Hippo signaling pathway ,030219 obstetrics & reproductive medicine ,Stem Cells ,Rehabilitation ,Obstetrics and Gynecology ,Cell Differentiation ,Coculture Techniques ,Menstruation ,CTGF ,Reproductive Medicine ,Culture Media, Conditioned ,Transcriptional Coactivator with PDZ-Binding Motif Proteins ,Cancer research ,Trans-Activators ,Female ,Stem cell ,Stromal Cells ,Wound healing ,Myofibroblast ,Transforming growth factor ,Signal Transduction - Abstract
Study question Can menstrual stem cells (MenSCs) inhibit myofibroblast differentiation and reverse transforming growth factor β (TGFβ)-mediated activation of myofibroblast phenotypes in human endometrial stromal cells (ESCs)? Summary answer MenSCs suppressed endometrial myofibroblast differentiation and reversed TGFβ-mediated activation of myofibroblast phenotypes, which might be associated with activation of the Hippo/TAZ pathway. What is known already The potential effect of MenSCs as a cell therapy include attenuation of intrauterine adhesions, but the underlying mechanisms by which MenSCs exerts these effects are not entirely understood. Study design, size, duration We evaluated the antagonistic effects of MenSCs on myofibroblast differentiation as well as the broader effect of the Hippo/TAZ signaling pathway on TGFβ-mediated induction of myofibroblast gene expression. The study design was based on a cohort of clinical proliferative phase endometrial samples obtained from three healthy premenopausal females with regular menstrual cycles. Participants/materials, setting, methods ESCs were cocultured with MenSCs or in MenSC-conditioned medium. Fibrotic markers (αSMA, collagen I, CTGF and fibronectin) as well as proliferation and wound-healing abilities were evaluated. Components of the Hippo/TAZ pathway (TAZ, p-TAZ, MOB1, p-MOB1, LATS1 and p-LATS1) were also investigated. Cell Counting Kit 8, wound healing assay, real-time PCR, western blotting, immunofluorescence and shRNA knockdown approaches were used to validate the findings. Main results and the role of chance MenSCs inhibited myofibroblast activation, resulting in more rapid proliferation of ESCs. MenSCs downregulated the expression of myofibroblast markers αSMA and collagen I and promoted endometrial wound healing. Coculture with MenSCs also attenuated the TGFβ-mediated increase in expression of fibrotic marker genes αSMA, collagen I, CTGF and fibronectin, and restored the wound-healing ability inhibited by TGFβ. MenSCs induced Hippo/TAZ pathway activation, resulting in nuclear export and cytoplasmic retention of TAZ. TAZ inhibition was demonstrated to have similar effects even in the absence of MenSCs, and inhibition of TAZ was sufficient to attenuate TGFβ-mediated myofibroblast activation. Large scale data N/A. Limitations, reasons for caution This study included only in vitro experiments. Thus, additional data from in vivo experiments are needed in a future study. Wider implications of the findings The Hippo/TAZ pathway may be an important therapeutic target for endometrial fibrosis. Study funding/competing interest(s) This study was supported by the National Natural Science Foundation of China (No. 81601236) and Zhejiang Provincial Natural Science Foundation of China (LY19H040009). None of the authors has any competing interests to declare.
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- 2018
13. Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer
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Bo Wang, Guoping Ren, Yanling Zhang, Chengli Du, Yue Sun, and Xiaoyan Liu
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Male ,Biophysics ,EEF1A2 ,Apoptosis ,Biology ,Biochemistry ,Prostate cancer ,Peptide Elongation Factor 1 ,Western blot ,Prostate ,Tumor Cells, Cultured ,medicine ,Humans ,Translation factor ,Molecular Biology ,Aged ,Cell Proliferation ,Aged, 80 and over ,medicine.diagnostic_test ,Cell growth ,Prostatic Neoplasms ,Cell Biology ,Middle Aged ,medicine.disease ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Cancer research ,Immunohistochemistry ,Apoptosis Regulatory Proteins - Abstract
Background eEF1A2 is a protein translation factor involved in protein synthesis, which possesses important function roles in cancer development. This study aims at investigating the expression pattern of eEF1A2 in prostate cancer and its potential role in prostate cancer development. Methods We examined the expression level of eEF1A2 in 30 pairs of prostate cancer tissues by using RT-PCR and immunohistochemical staining (IHC). Then we applied siRNA specifically targeting eEF1A2 to down-regulate its expression in DU-145 and PC-3 cells. Flow cytometer was used to explore apoptosis and Western-blot was used to detect the pathway proteins of apoptosis. Results Our results showed that the expression level of eEF1A2 in prostate cancer tissues was significantly higher compared to their corresponding normal tissues. Reduction of eEF1A2 expression in DU-145 and PC-3 cells led to a dramatic inhibition of proliferation accompanied with enhanced apoptosis rate. Western blot revealed that apoptosis pathway proteins (caspase3, BAD, BAX, PUMA) were significantly up-regulated after suppression of eEF1A2. More importantly, the levels of eEF1A2 and caspase3 were inversely correlated in prostate cancer tissues. Conclusion Our data suggests that eEF1A2 plays an important role in prostate cancer development, especially in inhibiting apoptosis. So eEF1A2 might serve as a potential therapeutic target in prostate cancer.
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- 2014
14. Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways
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Xiao-na Lin, Haiyan Zhu, Yanling Zhang, Xiaoxiao Hu, Yinshen Jiang, Songying Zhang, and Yongdong Dai
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0301 basic medicine ,Male ,Embryology ,Angiogenesis ,MAP Kinase Signaling System ,Neovascularization, Physiologic ,Biology ,Endometrium ,Mesenchymal Stem Cell Transplantation ,Neovascularization ,Andrology ,03 medical and health sciences ,Mice ,Endocrinology ,Cell Movement ,medicine ,Electrocoagulation ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Protein kinase B ,Cell Proliferation ,Mice, Inbred ICR ,Mesenchymal stem cell ,Obstetrics and Gynecology ,Mesenchymal Stem Cells ,Cell Biology ,Menstruation ,Transplantation ,Vascular endothelial growth factor A ,030104 developmental biology ,medicine.anatomical_structure ,Reproductive Medicine ,Infertility ,Immunology ,Female ,Stem cell ,medicine.symptom ,Proto-Oncogene Proteins c-akt - Abstract
Intrauterine adhesions are common acquired endometrial syndromes secondary to endometrial injury, with limited effective therapies. Recently, several studies have reported that bone marrow stem cells (BMSCs) could repair injured endometrium in animal experiments. However, the role of stem cells in endometrial injury repair and its therapeutic mechanisms remain unclear. Here, we established mouse endometrial injury model and examined the benefit of human endometrial mesenchymal stem cells derived from menstrual blood (MenSCs) in restoration of injured endometrium. Injured endometrium exhibited significantly accelerated restoration at Day 7 after MenSCs transplantation, with increased endometrial thickness and microvessel density. Moreover, the fertility of mice with injured endometrium was improved, with higher conception rate (53.57% vs 14.29%,P = 0.014) and larger embryo number (3.1 ± 0.6 vs 0.9 ± 0.7,P = 0.030) in MenSCs group than control group, while no difference was found in undamaged horns between two groups. Conditioned medium from MenSCs (MenSCs-CM) could decrease H2O2-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and promote proliferation, migration and angiogenesis. Angiogenesis effect of MenSCs-CM was also confirmed in Matrigel plug assay in mice. Furthermore, we discovered that MenSCs-CM could activate AKT and ERK pathways and induce the overexpression ofeNOS,VEGFA,VEGFR1,VEGFR2andTIE2in HUVECs, which are critical in MenSCs-CM-induced angiogenesis. Angiogenesis induced by MenSCs-CM could be reversed by inhibitors of AKT and/or ERK. Taken together, we concluded that MenSCs could restore injured endometrium and improve the fertility of the endometrial injury mice, which was partially attributed to angiogenesis induced by MenSCs.
- Published
- 2016
15. Delivery of megsin siRNA plasmid reveals therapeutic potential against diabetic nephropathy by down-regulating p27kip1 level
- Author
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Shana Zhai, Baoxing Wang, Yonghong Shi, Yanqing Chi, Yanling Zhang, Ying Li, and Maodong Liu
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Collagen Type IV ,Male ,Time Factors ,Blotting, Western ,Down-Regulation ,Transfection ,Nephrectomy ,Diabetes Mellitus, Experimental ,Diabetic nephropathy ,Mice ,Type IV collagen ,Animals ,Medicine ,Diabetic Nephropathies ,RNA, Small Interfering ,Cells, Cultured ,Serpins ,Cell Proliferation ,Tissue Inhibitor of Metalloproteinase-2 ,business.industry ,Cell growth ,Genetic Therapy ,Streptozotocin ,medicine.disease ,Molecular biology ,In vitro ,Blot ,Proteinuria ,Nephrology ,Lipofectamine ,Creatinine ,Mesangial Cells ,Cancer research ,Matrix Metalloproteinase 2 ,RNA Interference ,business ,Cyclin-Dependent Kinase Inhibitor p27 ,medicine.drug - Abstract
BACKGROUND Diabetic nephropathy is a complex disease with poor outcomes, and our current treatment measures are limited. It is urgent to search for novel therapeutic targets. Recently, a mesangium-predominant gene, megsin, has emerged as a participant in mesangial cell proliferation and/or mesangial matrix expansion. This study investigated the effect of megsin down-regulation on the progression of diabetic nephropathy. METHODS Streptozotocin (STZ)-induced diabetic CD-1 mice after uninephrectomy received a pBAsi mU6 Neo megsin siRNA plasmid for 12 weeks and were compared with age-matched nondiabetic mice. In vitro mouse mesangial cells were transfected with pBAsi mU6 Neo megsin siRNA plasmid using Lipofectamine 2000 reagent and further cultured in DMEM containing high glucose for up to 48 hours. All of the cells were collected for protein extraction and the supernatant for type IV collagen measurement. The expression of megsin, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteases-2 (TIMP-2) and p27(Kip1) was determined by Western blotting. RESULTS The megsin siRNA plasmid alleviated proteinuria and glomerular type IV collagen accumulation 12 weeks after the STZ injection, down-regulated renal cell proliferation and normalized the imbalance between MMP-2 and TIMP-2. Also, in vitro experiments showed that the glomerular mesangial cellular proliferation and type IV collagen production induced by high glucose were relieved after the transfection of megsin siRNA plasmid. The level of p27(kip1) was down-regulated in transfected mesangial cells significantly. CONCLUSIONS The study suggests that the down-regulation of megsin might exert beneficial effects on the diabetic kidney partly through down-regulation of p27(kip1) level and that megsin may serve as a novel therapeutic target in the management of diabetic nephropathy.
- Published
- 2011
16. Clonogenically Culturing and Expanding CD34+ Liver Cancer Stem Cells in Vitro
- Author
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Huaijun Zhou, Mark A. Zern, Yuyou Duan, Su Cheol Park, Neil D. Theise, Jong Ryeol Eun, Yanling Zhang, Benjamin Tschudy-Seney, Changjun Zeng, Yanghong Zhang, Rajendra Ramsamooj, Min Zhao, and Ngoc Tue Nguyen
- Subjects
Cutting-Edge Communication ,Technology ,Liver Stem Cell ,Antigens, CD34 ,Mice, SCID ,Stem cell marker ,Medical and Health Sciences ,Mice ,Stem Cell Research - Nonembryonic - Human ,Mice, Inbred NOD ,Cancer ,education.field_of_study ,Tumor ,Liver Neoplasms ,Hematology ,Biological Sciences ,Neoplastic Stem Cells ,Stem Cell Research - Nonembryonic - Non-Human ,Stem cell ,Carcinoma, Hepatocellular ,Immunology ,Population ,Biology ,SCID ,Cell Line ,Kruppel-Like Factor 4 ,SOX2 ,Clinical Research ,Cancer stem cell ,Cell Line, Tumor ,Biomarkers, Tumor ,Animals ,Humans ,CD90 ,Antigens ,education ,Cell Proliferation ,Carcinoma ,CD44 ,Hepatocellular ,Cell Biology ,Stem Cell Research ,biology.protein ,Cancer research ,Inbred NOD ,CD34 ,Digestive Diseases ,Biomarkers ,Developmental Biology - Abstract
© Copyright 2015, Mary Ann Liebert, Inc. A large number of cancer stem cells (CSCs) have been isolated and identified; however, none has been cultured in an unlimited manner in vitro without losing tumorigenicity and multipotency. In this study, we successfully clonogenically cultured a newly identified CD34 + liver CSC (LCSC) on feeder cells up to 22 passages (to date) without losing CSC property. Cloned CD34 + LCSC formed a round packed morphology and it could also be cryopreserved and recultured. Stem cell markers, CD34, CD117, and SOX2; normal liver stem cell markers, alpha fetoprotein, CK19, CK18, and OV6; putative CSC markers, CD44, CD133, EpCAM, and CD90; as well as CD31 were expressed in cloned CD34 + LCSC. SOX2 was the major factor in maintaining this LCSC before colonization, and interestingly, OCT4, SOX2, NAONG, Klf4, c-Myc, and Lin28 were upregulated in association with symmetric self-renewal for colony growth of CD34 + LCSC on feeder cells. Gene expression patterns of in vitro differentiation were consistent with our in vivo finding; furthermore, the tumorigenicity of cloned CD34 + LCSC was not different from uncloned CD34 + LCSC sorted from parental PLC. These results show that our cloned CD34 + LCSC maintained CSC property, including self-renewal, bipotency, and tumorigenicity after long-term culture, demonstrating that this LCSC can be cultured in an unlimited manner in vitro. Thus, establishing pure population of CSCs isolated from the patients will provide an opportunity to explore the mechanisms of tumorigenesis and cancer development, and to identify unique biomarkers presenting potential indicators of drug efficacy against CSCs for establishment of a novel strategy for cancer therapy.
- Published
- 2015
17. The Critical Role of Rab31 in Cell Proliferation and Apoptosis in Cancer Progression
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Yan Liu, Yanling Zhang, Junyuan Yan, Lijun Chen, Yunyan Pan, and Yanlin Feng
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0301 basic medicine ,Male ,Epithelial-Mesenchymal Transition ,Cyclin A ,Neuroscience (miscellaneous) ,Mice, Nude ,Apoptosis ,Biology ,S Phase ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Cyclin D1 ,Cell Movement ,Cell Line, Tumor ,Cyclins ,Neoplasms ,medicine ,Animals ,Humans ,Cyclin B1 ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Cell growth ,G1 Phase ,Cancer ,medicine.disease ,030104 developmental biology ,Neurology ,rab GTP-Binding Proteins ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Immunology ,Cancer cell ,Cancer research ,biology.protein ,Disease Progression ,Mitogen-Activated Protein Kinases ,Proto-Oncogene Proteins c-akt - Abstract
Rab31, a member of the Ras superfamily, is reported to play a role in tumor development and progression. However, the detailed role of Rab31 in proliferation and apoptosis of cancer cells is still unclear. Here, we used different cell lines, such as glioblastoma, and cervical cancer, to investigate the role of Rab31 in cancer progression. We found that Rab31 promotes U87 and SiHa cell proliferation via activation of G1/S checkpoint transitions, accompanied with an increase of cyclin D1, cyclin A, and cyclin B1. Meanwhile, Rab31 inhibits U87 and SiHa cell apoptosis, and decreased the BAX and PIG3 expression, but enhanced BCL2 expression. In addition, Rab31 induces N-cadherin, Vimentin, and Snail expression, and inhibits E-cadherin expression to regulate proliferation and migration. Besides, we observed that ERK1/2 and PI3k/AKT pathways are required for Rab31-induced cell proliferation and migration. In vivo, the knockdown of Rab31 suppresses tumor mass growth. In conclusion, our data highlight the crucial role of Rab31 in cancer progression, proliferation, and apoptosis, and indicates that Rab31 may be a useful and effective target for the clinical therapy of most cancers.
- Published
- 2015
18. Therapeutic Approach for Diabetic Nephropathy Using Gene Delivery of Translocase of Inner Mitochondrial Membrane 44 by Reducing Mitochondrial Superoxide Production
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Kenichi Shikata, Jun Eguchi, Jun Wada, Akihiro Yasuhara, Izumi Hashimoto, Hirofumi Makino, Yanling Zhang, and Yashpal S. Kanwar
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Male ,medicine.medical_specialty ,Apoptosis ,Mitochondrion ,Gene delivery ,Kidney ,Mitochondrial Membrane Transport Proteins ,Mitochondrial apoptosis-induced channel ,Cell Line ,Membrane Potentials ,Mitochondrial Proteins ,Superoxide dismutase ,Mice ,Adenosine Triphosphate ,Superoxides ,Internal medicine ,Mitochondrial Precursor Protein Import Complex Proteins ,medicine ,Animals ,Humans ,Diabetic Nephropathies ,Inner mitochondrial membrane ,Cell Proliferation ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Superoxide Dismutase ,Membrane Proteins ,Genetic Therapy ,General Medicine ,Recombinant Proteins ,Mitochondria ,Cell biology ,Glutathione Reductase ,Endocrinology ,chemistry ,Nephrology ,DNAJA3 ,biology.protein ,ATP–ADP translocase ,Carrier Proteins - Abstract
Hyperglycemia-induced overproduction of mitochondrial reactive oxygen species has emerged as a major player in diabetic vascular complications. Mammalian translocase of inner mitochondrial membrane 44 (TIM44) was identified by upregulation in diabetic mouse kidneys. TIM44 functions as a membrane anchor of mitochondrial heat-shock protein 70 (mtHsp70) to TIM23 complex and is involved in the import of mitochondria-targeted preproteins into mitochondrial matrix. The process is dependent on inner membrane potential and ATP hydrolysis on ATPase domain of mitochondrial heat-shock protein 70. Hemagglutination virus of Japan-envelope vector that carries pcDNA3.1 plasmid that contains the full-length cDNA of TIM44 and control plasmid were injected weekly into the tail vein of uninephrectomized streptozotocin-induced diabetic CD-1 mice. The gene delivery alleviated proteinuria and renal hypertrophy at 8 wk after the injection, inhibited renal cell proliferation and apoptosis, and suppressed superoxide production. In vitro experiments, using human proximal tubular (HK2) cells, revealed that the gene delivery of TIM44 reversed high glucose-induced metabolic and cellular abnormalities such as enhanced reactive oxygen species production, increased ATP contents, alterations in inner membrane potential, increased cell proliferation, and apoptosis. Transfection with siRNA and expressing vector of TIM44 revealed that TIM44 facilitates import of antioxidative enzymes such as superoxide dismutase and glutathione peroxidase into mitochondria. The gene delivery of TIM44 therefore seems to be beneficial for the maintenance of mitochondrial function and is a novel therapeutic approach for diabetic nephropathy.
- Published
- 2006
19. Dual drugs (microRNA-34a and paclitaxel)-loaded functional solid lipid nanoparticles for synergistic cancer cell suppression
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Lu Han, Yanling Zhang, Hongxin Shen, Li Deng, Sanjun Shi, Zhirong Zhang, Xun Sun, and Tao Gong
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Paclitaxel ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,Pharmacology ,chemistry.chemical_compound ,Mice ,Drug Delivery Systems ,In vivo ,Cell Line, Tumor ,Solid lipid nanoparticle ,Medicine ,Animals ,Humans ,Tissue Distribution ,Lung cancer ,Cell Proliferation ,business.industry ,Melanoma ,Cancer ,Drug Synergism ,medicine.disease ,Antineoplastic Agents, Phytogenic ,MicroRNAs ,Hyaluronan Receptors ,chemistry ,MicroRNA 34a ,Drug Design ,Cancer cell ,Nanoparticles ,business - Abstract
A co-delivery system that can transport cancer related microRNAs and chemotherapeutics to their distinct targets in the tumors is an attractive strategy to eliminate tumor relapse in lung cancer therapy. In this study, we developed a dual-drug delivery system for an endogenous microRNA (miR-34a) and paclitaxel (PTX) for synergistic cancer therapy. PTX (a meiotic inhibitor) and miR-34a were loaded into cationic solid lipid nanoparticles (miSLNs-34a/PTX) which were used to treat murine B16F10-CD44(+) melanoma metastasized to the lungs of mice. This nanoparticle system demonstrated good protection for miR-34a and PTX from degradation in the serum, and had an average size of approximately 220 nm by photon correlation spectroscopy (PCS). In vitro, the parallel activity of PTX and miR-34a show synergistic anticancer efficacy. In vivo, miSLNs-34a/PTX showed passive targetability to the tumor-bearing lung tissues, and was demonstrated to be much more potent in inhibition of B16F10-bearing tumor growth and elimination of cancer cell populations in the lung than single drug-loaded solid lipid nanoparticles. It has been shown that such co-delivery of miR-34a and PTX is promising for enhanced cancer therapy to reduce tumor relapse.
- Published
- 2014
20. Cell-based assay system to estimate the effect of 125I seeds on cancer cells: effect of osteopontin
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Sheng Peng, Fujun Zhang, Yanling Zhang, Fei Gao, Zhenyin Liu, Tao Zhang, Mingjian Lu, and Guang Yang
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Cancer Research ,Pathology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Brachytherapy ,Motility ,Apoptosis ,In Vitro Techniques ,Iodine Radioisotopes ,Western blot ,Cell Movement ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Pharmacology (medical) ,Osteopontin ,Cell Proliferation ,biology ,medicine.diagnostic_test ,Cell growth ,Liver Neoplasms ,food and beverages ,General Medicine ,In vitro ,Cell biology ,Oncology ,Cell culture ,Cancer cell ,biology.protein ,Signal Transduction - Abstract
Background and Purpose: A number of recent patents related to 125I seed and osteopontin have been awarded. In this study, we developed a new in vitro model to study the radiobiological effects of 125I seeds on cancer cells. Methods: We placed 125I seeds in a cell culture plate with cells seeded on a transwell chamber to evaluate the effects of 125I seeds on cell motility. We placed 125I seeds in a transwell chamber with cells seeded on the cell culture plate to study cell proliferation, apoptosis, and to perform western blot. Results: We used SK-Hep-1 liver cancer cells to evaluate the effectiveness of our model, and investigated the role of osteopontin in the therapeutic effects of 125I seeds. We found that 125I seeds inhibited the cell proliferation and motility in this model while osteopontin reduced these effects. We also measured the effects of 125I seeds on apoptosis. Furthermore, when treated with 125I seeds, we detected changes in several signaling pathways that are involved in the proliferation and invasion of cancer cells. Conclusions: The model can be used to assess the biological effects of 125I seeds in vitro. Osteopontin may be involved in the 125I seed-induced inhibition of SK-Hep-1 cells.
- Published
- 2014
21. Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects on Tumor in Vitro
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Shifeng Wang, Yangyang Yu, Sheng-Nan Sun, Yanling Zhang, Qiao Zhang, Yanjiang Qiao, Wei Yang, Shiyou Li, and Yuxin Zhang
- Subjects
0301 basic medicine ,Drug Evaluation, Preclinical ,Pharmacology ,lcsh:Chemistry ,HeLa ,0302 clinical medicine ,Neoplasms ,Myocytes, Cardiac ,Receptor ,lcsh:QH301-705.5 ,Spectroscopy ,Cell Death ,General Medicine ,Receptor, Endothelin A ,Endothelin A Receptor Antagonists ,Computer Science Applications ,030220 oncology & carcinogenesis ,Lactates ,Salvianolic acid A ,endothelin A receptor ,anticancer ,antagonist ,cardiotoxicity ,Induced Pluripotent Stem Cells ,Biology ,Cardiotoxins ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Caffeic Acids ,DU145 ,Cell Line, Tumor ,parasitic diseases ,Human Umbilical Vein Endothelial Cells ,Humans ,Physical and Theoretical Chemistry ,Autocrine signalling ,Molecular Biology ,Cell Proliferation ,A549 cell ,Cell growth ,Organic Chemistry ,Reproducibility of Results ,biology.organism_classification ,HEK293 Cells ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cell culture - Abstract
Endothelin-1 (ET-1) autocrine and paracrine signaling modulate cell proliferation of tumor cells by activating its receptors, endothelin A receptor (ETAR) and endothelin B receptor (ETBR). Dysregulation of ETAR activation promotes tumor development and progression. The potential of ETAR antagonists and the dual-ETAR and ETBR antagonists as therapeutic approaches are under preclinical and clinical studies. Salvianolic acid A (Sal A) is a hydrophilic polyphenolic derivative isolated from Salvia miltiorrhiza Bunge (Danshen), which has been reported as an anti-cancer and cardio-protective herbal medicine. In this study, we demonstrate that Sal A inhibits ETAR activation induced by ET-1 in both recombinant and endogenous ETAR expression cell lines. The IC50 values were determined as 5.7 µM in the HEK293/ETAR cell line and 3.14 µM in HeLa cells, respectively. Furthermore, our results showed that Sal A suppressed cell proliferation and extended the doubling times of multiple cancer cells, including HeLa, DU145, H1975, and A549 cell lines. In addition, Sal A inhibited proliferation of DU145 cell lines stimulated by exogenous ET-1 treatment. Moreover, the cytotoxicity and cardio-toxicity of Sal A were assessed in human umbilical vein endothelial cells (HUVEC) and Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which proved that Sal A demonstrates no cytotoxicity or cardiotoxicity. Collectively, our findings indicate that Sal A is a novel anti-cancer candidate through targeting ETAR.
- Published
- 2016
22. Effects of angiotensin II type 2 receptor overexpression on the growth of hepatocellular carcinoma cells in vitro and in vivo
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Yi Zhang, Zhibing Liang, Jinlong Li, Hongyan Du, Hongwei Li, Yang Fei, Andrew Li, Zhi Huang, Baihong Chen, Nana Pei, Feilong Jie, Colin Sumners, Yanling Zhang, Suihai Wang, and Ming Li
- Subjects
MAPK/ERK pathway ,Cancer Treatment ,lcsh:Medicine ,Apoptosis ,medicine.disease_cause ,Immunoenzyme Techniques ,Mice ,Molecular Cell Biology ,Basic Cancer Research ,Tumor Cells, Cultured ,Signaling in Cellular Processes ,Membrane Receptor Signaling ,lcsh:Science ,Apoptotic Signaling Cascade ,Apoptotic Signaling ,Mice, Inbred BALB C ,Multidisciplinary ,Cell Death ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Cycle ,Liver Neoplasms ,Gene Therapy ,Cell cycle ,Signaling Cascades ,Oncology ,Medicine ,Cell Division ,Research Article ,Signal Transduction ,Carcinoma, Hepatocellular ,Blotting, Western ,Immunology ,Mice, Nude ,In Vitro Techniques ,Biology ,Real-Time Polymerase Chain Reaction ,Receptor, Angiotensin, Type 2 ,Cell Growth ,Adenoviridae ,In vivo ,Gastrointestinal Tumors ,medicine ,Animals ,Humans ,RNA, Messenger ,Cell Proliferation ,Inflammation ,Cell growth ,lcsh:R ,Immunity ,Cancers and Neoplasms ,Hepatocellular Carcinoma ,Xenograft Model Antitumor Assays ,Molecular biology ,Angiotensin II ,digestive system diseases ,Cell culture ,Cancer research ,lcsh:Q ,Carcinogenesis - Abstract
Increasing evidence suggests that the renin-angiotensin system (RAS) plays an important role in tumorigenesis. The interaction between Angiotensin II (AngII) and angiotensin type 1 receptor (AT1R) may have a pivotal role in hepatocellular carcinoma (HCC) and therefore, AT1R blocker and angiotensin I-converting enzyme (ACE) inhibitors may have therapeutic potential in the treatment of hepatic cancer. Although the involvement of AT1R has been well explored, the role of the angiotensin II Type 2 receptor (AT2R) in HCC progression remains poorly understood. Thus, the aim of this study was to explore the effects of AT2R overexpression on HCC cells in vitro and in mouse models of human HCC. An AT2R recombinant adenoviral vector (Ad-G-AT2R-EGFP) was transduced into HCC cell lines and orthotopic tumor grafts. The results indicate that the high dose of Ad-G-AT2R-EGFP–induced overexpression of AT2R in transduced HCC cell lines produced apoptosis. AT2R overexpression in SMMC7721 cells inhibited cell proliferation with a significant reduction of S-phase cells and an enrichment of G1-phase cells through changing expression of CDK4 and cyclinD1. The data also indicate that overexpression of AT2R led to apoptosis via cell death signaling pathway that is dependent on activation of p38 MAPK, pJNK, caspase-8 and caspase-3 and inactivation of pp42/44 MAPK (Erk1/2). Finally, we demonstrated that moderately increasing AT2R expression could increase the growth of HCC tumors and the proliferation of HCC cells in vivo. Our findings suggest that AT2R overexpression regulates proliferation of hepatocellular carcinoma cells in vitro and in vivo, and the precise mechanisms of this phenomenon are yet to be fully determined.
- Published
- 2013
23. In Vivo Delivery of Gremlin siRNA Plasmid Reveals Therapeutic Potential against Diabetic Nephropathy by Recovering Bone Morphogenetic Protein-7
- Author
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Yonghong Shi, Sandra M. Malakauskas, Jun Wada, Huijun Duan, Yanling Zhang, Chunyang Du, Yunzhuo Ren, Qingxian Zhang, Yingmin Li, Maodong Liu, and Ying Li
- Subjects
Male ,Smad5 Protein ,Small interfering RNA ,Bone Morphogenetic Protein 7 ,Blotting, Western ,lcsh:Medicine ,Apoptosis ,Enzyme-Linked Immunosorbent Assay ,SMAD ,Bone morphogenetic protein ,Diabetic nephropathy ,Diabetes and Endocrinology/Obesity ,Mice ,medicine ,In Situ Nick-End Labeling ,Animals ,Immunoprecipitation ,Diabetic Nephropathies ,RNA, Small Interfering ,lcsh:Science ,Cells, Cultured ,Cell Proliferation ,Multidisciplinary ,Chemistry ,Reverse Transcriptase Polymerase Chain Reaction ,lcsh:R ,Transfection ,medicine.disease ,Molecular biology ,Immunohistochemistry ,Bone morphogenetic protein 7 ,Diabetes and Endocrinology ,Cancer research ,Cytokines ,Intercellular Signaling Peptides and Proteins ,lcsh:Q ,Gremlin (protein) ,Diabetes and Endocrinology/Type 1 Diabetes ,Transforming growth factor ,Research Article ,Plasmids - Abstract
Diabetic nephropathy is a complex and poorly understood disease process, and our current treatment options are limited. It remains critical, then, to identify novel therapeutic targets. Recently, a developmental protein and one of the bone morphogenetic protein antagonists, Gremlin, has emerged as a novel modulator of diabetic nephropathy. The high expression and strong co-localization with transforming growth factor-beta1 in diabetic kidneys suggests a role for Gremlin in the pathogenesis of diabetic nephropathy. We have constructed a gremlin siRNA plasmid and have examined the effect of Gremlin inhibition on the progression of diabetic nephropathy in a mouse model. CD-1 mice underwent uninephrectomy and STZ treatment prior to receiving weekly injections of the plasmid. Inhibition of Gremlin alleviated proteinuria and renal collagen IV accumulation 12 weeks after the STZ injection and inhibited renal cell proliferation and apoptosis. In vitro experiments, using mouse mesangial cells, revealed that the transfect ion of gremlin siRNA plasmid reversed high glucose induced abnormalities, such as increased cell proliferation and apoptosis and increased collagen IV production. The decreased matrix metalloprotease level was partially normalized by transfection with gremlin siRNA plasmid. Additionally, we observed recovery of bone morphogenetic protein-7 signaling activity, evidenced by increases in phosphorylated Smad 5 protein levels. We conclude that inhibition of Gremlin exerts beneficial effects on the diabetic kidney mainly through maintenance of BMP-7 activity and that Gremlin may serve as a novel therapeutic target in the management of diabetic nephropathy.
- Published
- 2010
24. Chemical constituents of stems and branches of Adina polycephala
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Sujuan Wang, Jiangong Shi, Jin-Feng Hu, Chenggen Zhu, Maoluo Gan, Shuai Li, Yanling Zhang, Yongchun Yang, and Nai-Hong Chen
- Subjects
Molecular Structure ,Plant Stems ,biology ,Plant Extracts ,Chemistry ,Rubiaceae ,biology.organism_classification ,Rats ,Complementary and alternative medicine ,Cell Line, Tumor ,Chemical constituents ,Botany ,Animals ,Humans ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Adina ,Cell Proliferation - Abstract
To investigate chemical constituents of the stems and branches of Adina polycephala and their pharmacological activities.The constituents were isolated by a combination of various chromatographic techniques including column chromatography on silica gel, Sephadex LH-20, and C-18, as well as reversed-phase HPLC. Structures of the isolates were identified by spectroscopic data analysis. In vitro cytotoxic, anti-inflammatory, anti-oxidant, anti-HIV, neuroprotective and anti-diabetic activities were screened by using cell-based models.Twenty-eight constituents were isolated. Their structures were identified as clemochinenoside B (1), kelampayoside A (2), osmanthuside H (3), 4-hydroxy-3-methoxyphenol-beta-D-[6-O-(4-hydroxy-3,5-dimethoxylbenzoate)]-glucopyranoside (4), and syringic acid beta-D-glucopyranosyl ester (5). Ten iridoidal glycosides: geniposidic acid (6), geniposide (7), 6beta-hydroxygeniposide (8), 6beta-hydroxygeniposide (9), ixoside (10), ixoside 11-methyl ester (11), 11-methyl forsythide (12), 7beta-hydroxysplendoside (13), gardoside (14) and mussaenosidic acid (15), (+) -pinoresinol (16), (+) -medioresinol (17), (+) -syringaresinol (18), (-)-lariciresinol (19), evofolin-B (20), alpha-hydroxyacetovaillone (21), syringic acid (22), vanillin (23), 3, 4, 5-trimethoxyphenol (24), and 2,6-dimethoxy-1, 4-benzoquinone (25), beta-sitosterol (26), mannitol (27), and daucosterol (28). At a concentration of 1.0 x 10(-5) mol x L(-1), these compounds were inactive in the assays, including cytotoxicity against human tumor cell lines (HCT-8, Bel-7402, BGC-823, A549 and A2780), anti-inflammatory activity against the release of beta-glucuronidase in rat polymorphonuclear leukocytes (PMNs) induced by platelet-activating factor (PAF), antioxidant activity in Fe(2+)-cystine-induced rat liver microsomal lipid peroxidation, anti-HIV activity against HIV-1 replication, neuroprotective activity against serum deprivation or glutamate induced neurotoxicity in cultures of PC12 cells, and the inhibitory activity against protein tyrosine phosphatase 1B (PTP1B).Compounds 1-20 were obtained from the genus Adina for the first time. The 13C-NMR data of compounds 10 and 11 were reassigned. A further evaluation of pharmacological activity of these compounds is expected.
- Published
- 2010
25. Biocompatibility of polypropylene mesh scaffold with adipose-derived stem cells.
- Author
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HUI CHENG, YANLING ZHANG, BEI ZHANG, JIE CHENG, WEIQI WANG, XIN TANG, PENG TENG, and YANYU LI
- Subjects
- *
POLYPROPYLENE , *COLLAGENASES , *CELL proliferation , *FLOW cytometry , *NEOVASCULARIZATION - Abstract
In this study, we investigated the rejection of the synthetic patch and human tissues in the host. We observed the growth of adipose-derived stem cells (ADSCs) cultured with polypropylene mesh in vitro. The results of flow cytometry showed that the expression of CD44, CD73, CD90, CD45, CD14 and CD34 was 98.54, 95.32, 98.49, 1.21, 3.01 and 2.14%, respectively. ADSCs were isolated from rabbit subcutaneous adipose tissue after collagenase digestion, filtration and centrifugation. The ADSCs of passage 3 were seeded onto the polypropylene mesh scaffolds. New Zealand White female breeder rabbits were implanted with polypropylene mesh, ADSC-fixed polypropylene mesh in the abdomen. After 4 weeks, adhesion was performed and the erosion of the mesh was evaluated. It was found that polypropylene mesh, ADSC-fixed polypropylene mesh all had different degrees of corrosion, and adhesion, but polypropylene mesh was more corroded. ADSC-fixed polypropylene mesh induced a milder chronic inflammation response compared with polypropylene, had significantly lower scores for inflammation (t=11.083), and had significantly higher scores for neovascularization (t=14.362) and fibroblastic proliferation (t=15.979). The relative amount of VEGF mRNA was significantly lower for ADSCfixed polypropylene compared with the other polypropylene meshes (t=94.6). In conclusion, polypropylene mesh scaffold with ADSCs exhibit excellent cellular compatibility and are promising in clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
26. Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects on Tumor in Vitro.
- Author
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Qiao Zhang, Shifeng Wang, Yangyang Yu, Shengnan Sun, Yuxin Zhang, Yanling Zhang, Wei Yang, Shiyou Li, and Yanjiang Qiao
- Subjects
PREPROENDOTHELIN ,PARACRINE mechanisms ,CANCER cells ,CELL proliferation ,CANCER invasiveness - Abstract
Endothelin-1 (ET-1) autocrine and paracrine signaling modulate cell proliferation of tumor cells by activating its receptors, endothelin A receptor (ET
A R) and endothelin B receptor (ETB R). Dysregulation of ETA R activation promotes tumor development and progression. The potential of ETAR antagonists and the dual-ETA R and ETB R antagonists as therapeutic approaches are under preclinical and clinical studies. Salvianolic acid A (Sal A) is a hydrophilic polyphenolic derivative isolated from Salvia miltiorrhiza Bunge (Danshen), which has been reported as an anti-cancer and cardio-protective herbal medicine. In this study, we demonstrate that Sal A inhibits ETA R activation induced by ET-1 in both recombinant and endogenous ETAR expression cell lines. The IC50 values were determined as 5.7 µM in the HEK293/ETAR cell line and 3.14 µM in HeLa cells, respectively. Furthermore, our results showed that Sal A suppressed cell proliferation and extended the doubling times of multiple cancer cells, including HeLa, DU145, H1975, and A549 cell lines. In addition, Sal A inhibited proliferation of DU145 cell lines stimulated by exogenous ET-1 treatment. Moreover, the cytotoxicity and cardio-toxicity of Sal A were assessed in human umbilical vein endothelial cells (HUVEC) and Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which proved that Sal A demonstrates no cytotoxicity or cardiotoxicity. Collectively, our findings indicate that Sal A is a novel anti-cancer candidate through targeting ETA R. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
27. The inhibitory effects of extracellular ATP on the growth of nasopharyngeal carcinoma cells via P2Y2 receptor and osteopontin.
- Author
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Guang Yang, Shenghong Zhang, Yanling Zhang, Qiming Zhou, Sheng Peng, Tao Zhang, Changfu Yang, Zhenyu Zhu, and Fujun Zhang
- Subjects
ADENOSINE triphosphate ,OSTEOPONTIN ,NASOPHARYNX cancer ,CELL migration ,FLOW cytometry ,CELL proliferation - Abstract
Background Nasopharyngeal carcinoma (NPC) is a common malignant tumor observed in the populations of southern China and Southeast Asia. However, little is known about the effects of purinergic signal on the behavior of NPC cells. This study analyzed the effects of ATP on the growth and migration of NPC cells, and further investigated the potential mechanisms during the effects. Methods Cell viability was estimated by MTT assay. Transwell assay was utilized to assess the motility of NPC cells. Cell cycle and apoptosis were detected by flow cytometry analysis. Changes in OPN, P2Y2 and p65 expression were assessed by western blotting analysis or immunofluorescence. The effects of ATP and P2Y2 on promoter activity of OPN were analyzed by luciferase activity assay. The binding of p65 to the promoter region of OPN was examined by ChIP assay. Results An MTT assay indicated that ATP inhibited the proliferation of NPC cells in time- and dosedependent manners, and a Transwell assay showed that extracellular ATP inhibited the motility of NPC cells. We further investigated the potential mechanisms involved in the inhibitory effect of extracellular ATP on the growth of NPC cells and found that extracellular ATP could reduce Bcl-2 and p-AKT levels while elevating Bax and cleaved caspase-3 levels in NPC cells. Decreased levels of p65 and osteopontin were also detected in the ATP-treated NPC cells. We demonstrated that extracellular ATP inhibited the growth of NPC cells via p65 and osteopontin and verified that P2Y2 overexpression elevated the inhibitory effect of extracellular ATP on the proliferation of NPC cells. Moreover, a dual luciferase reporter assay showed that the level of osteopontin transcription was inhibited by extracellular ATP and P2Y2. ATP decreased the binding of p65 to potential sites in the OPN promoter region in NPC cells. Conclusion This study indicated that extracellular ATP inhibited the growth of NPC cells via P2Y2, p65 and OPN. ATP could be a promising agent serving as an adjuvant in the treatment of NPC. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
28. In Vivo Delivery of Gremlin siRNA Plasmid Reveals Therapeutic Potential against Diabetic Nephropathy by Recovering Bone Morphogenetic Protein-7.
- Author
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Qingxian Zhang, Yonghong Shi, Jun Wada, Malakauskas, Sandra M., Maodong Liu, Yunzhuo Ren, Chunyang Du, Huijun Duan, Yingmin Li, Ying Li, and Yanling Zhang
- Subjects
KIDNEY disease treatments ,PEOPLE with diabetes ,SMALL interfering RNA ,MORPHOGENESIS ,PLASMIDS ,METALLOPROTEINASES ,IMMUNOMODULATORS ,CELL proliferation ,APOPTOSIS ,PROTEINURIA treatment - Abstract
Diabetic nephropathy is a complex and poorly understood disease process, and our current treatment options are limited. It remains critical, then, to identify novel therapeutic targets. Recently, a developmental protein and one of the bone morphogenetic protein antagonists, Gremlin, has emerged as a novel modulator of diabetic nephropathy. The high expression and strong co-localization with transforming growth factor- β1 in diabetic kidneys suggests a role for Gremlin in the pathogenesis of diabetic nephropathy. We have constructed a gremlin siRNA plasmid and have examined the effect of Gremlin inhibition on the progression of diabetic nephropathy in a mouse model. CD-1 mice underwent uninephrectomy and STZ treatment prior to receiving weekly injections of the plasmid. Inhibition of Gremlin alleviated proteinuria and renal collagen IV accumulation 12 weeks after the STZ injection and inhibited renal cell proliferation and apoptosis. In vitro experiments, using mouse mesangial cells, revealed that the transfection of gremlin siRNA plasmid reversed high glucose induced abnormalities, such as increased cell proliferation and apoptosis and increased collagen IV production. The decreased matrix metalloprotease level was partially normalized by transfection with gremlin siRNA plasmid. Additionally, we observed recovery of bone morphogenetic protein-7 signaling activity, evidenced by increases in phosphorylated Smad 5 protein levels. We conclude that inhibition of Gremlin exerts beneficial effects on the diabetic kidney mainly through maintenance of BMP-7 activity and that Gremlin may serve as a novel therapeutic target in the management of diabetic nephropathy. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
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