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https://www.readbyqxmd.com/read/28726783/kmt2a-promotes-melanoma-cell-growth-by-targeting-htert-signaling-pathway
#1
Changlin Zhang, Chen Song, Tianze Liu, Ranran Tang, Miao Chen, Fan Gao, Binyi Xiao, Ge Qin, Fen Shi, Wenbin Li, Yixin Li, Xiaoyan Fu, Dingbo Shi, Xiangsheng Xiao, Lan Kang, Wenlin Huang, Xiaojun Wu, Bing Tang, Wuguo Deng
Melanoma is an aggressive cutaneous malignancy, illuminating the exact mechanisms and finding novel therapeutic targets are urgently needed. In this study, we identified KMT2A as a potential target, which promoted the growth of human melanoma cells. KMT2A knockdown significantly inhibited cell viability and cell migration and induced apoptosis, whereas KMT2A overexpression effectively promoted cell proliferation in various melanoma cell lines. Further study showed that KMT2A regulated melanoma cell growth by targeting the hTERT-dependent signal pathway...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28723630/functional-role-of-setd2-bap1-parp-3-and-pbrm1-candidate-genes-on-the-regulation-of-htert-gene-expression
#2
Hannah Linne, Hemad Yasaei, Alison Marriott, Amanda Harvey, Kefah Mokbel, Robert Newbold, Terry Roberts
Narrowing the search for the critical hTERT repressor sequence(s) has identified three regions on chromosome 3p (3p12-p21.1, 3p21.2 and 3p21.3-p22). However, the precise location and identity of the sequence(s) responsible for hTERT transcriptional repression remains elusive. In order to identify critical hTERT repressor sequences located within human chromosome 3p12-p22, we investigated hTERT transcriptional activity within 21NT microcell hybrid clones containing chromosome 3 fragments. Mapping of chromosome 3 structure in a single hTERT-repressed 21NT-#3fragment hybrid clone, revealed a 490kb region of deletion localised to 3p21...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28717007/epigenetic-suppression-of-human-telomerase-htert-is-mediated-by-the-metastasis-suppressor-nme2-in-a-g-quadruplex-dependent-fashion
#3
Dhurjhoti Saha, Ankita Singh, Tabish Hussain, Vivek Srivastava, Suman Sengupta, Anirban Kar, Parashar Dhapola, Vishnu Dhople, Ramesh Ummani, Shantanu Chowdhury
Transcriptional activation of the human telomerase reverse transcriptase (hTERT) gene, which remains repressed in adult somatic cells, is critical during tumorigenesis. Several transcription factors and the epigenetic state of the hTERT promoter are known to be important for tight control of hTERT in normal tissues, but the molecular mechanisms leading to hTERT reactivation in cancer are not well understood. Surprisingly, here we found occupancy of the metastasis suppressor nonmetastatic 2 (NME2) within hTERT core promoter in HT1080 fibrosarcoma cells and HCT116 colon cancer cells, and NME2 mediated transcriptional repression of hTERT in these cells...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716107/biomarkers-of-resistance-to-radiation-therapy-a-prospective-study-in-cervical-carcinoma
#4
P Moreno-Acosta, A Vallard, S Carrillo, O Gamboa, A Romero-Rojas, M Molano, J Acosta, D Mayorga, C Rancoule, M A Garcia, M Cotes Mestre, N Magné
BACKGROUND: Clinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance. METHODS: The present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation...
July 17, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28713902/establishment-and-characterization-of-cell-lines-derived-from-complete-hydatidiform-mole
#5
Eiko Yamamoto, Kaoru Niimi, Tohru Kiyono, Toshimichi Yamamoto, Kimihiro Nishino, Kenichi Nakamura, Tomomi Kotani, Hiroaki Kajiyama, Kiyosumi Shibata, Fumitaka Kikkawa
Gestational trophoblastic diseases (GTDs) are a group of diseases characterized by abnormal cellular proliferation of atypical trophoblasts. A hydatidiform mole is an abnormal pregnancy caused by genetic fertilization disorders, and it can be classified as a complete hydatidiform mole (CHM) or a partial hydatidiform mole. The aim of this study was to establish cell lines from CHMs and to characterize the cells for future studies concerning GTD. HMol1-2C, HMol1-3B, HMol1-8 and HMol3-1B were established from primary cultures of CHM explants following the introduction of different combinations of genes including human telomerase reverse transcriptase (hTERT), a mutant form of CDK (CDK4R24C), cyclin D1, p53C234, MYC and HRAS...
July 14, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28706881/assessment-effects-of-resveratrol-on-human-telomerase-reverse-transcriptase-messenger-ribonucleic-acid-transcript-in-human-glioblastoma
#6
Azin Mirzazadeh, Majid Kheirollahi, Ehsan Farashahi, Fatemeh Sadeghian-Nodoushan, Mohammad Hasan Sheikhha, Behrouz Aflatoonian
BACKGROUND: Glioblastoma (GBM) is the most common and aggressive brain tumor, which has a poor prognosis despite the advent of different therapeutic strategies. There are numerous molecular biomarkers to contribute diagnosis, prognosis, and prediction of response to the current therapy in GBM. One of the most important markers that are potentially valuable is immortalization-specific or immortalization-associated marker named "hTERT messenger ribonucleic acid (mRNA)" the key subunit of telomerase enzyme, which is expressed in more than 85% of cancer cells, in spite of the majority of normal somatic cells...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28705199/the-m-phase-specific-hyperphosphorylation-of-staufen2-involved-the-cyclin-dependent-kinase-cdk1
#7
Rémy Beaujois, Elizabeth Ottoni, Xin Zhang, Christina Gagnon, Sami HSine, Stéphanie Mollet, Wildriss Viranaicken, Luc DesGroseillers
BACKGROUND: Staufen2 (STAU2) is an RNA-binding protein involved in the post-transcriptional regulation of gene expression. This protein was shown to be required for organ formation and cell differentiation. Although STAU2 functions have been reported in neuronal cells, its role in dividing cells remains deeply uncharacterized. Especially, its regulation during the cell cycle is completely unknown. RESULTS: In this study, we showed that STAU2 isoforms display a mitosis-specific slow migration pattern on SDS-gels in all tested transformed and untransformed cell lines...
July 14, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28704482/proteomic-identification-of-proteins-differentially-expressed-following-overexpression-of-htert-human-telomerase-reverse-transcriptase-in-cancer-cells
#8
Rishi Kumar Jaiswal, Pramod Kumar, Amod Sharma, Deepak Kumar Mishra, Pramod Kumar Yadava
Reverse transcriptase activity of telomerase adds telomeric repeat sequences at extreme ends of the newly replicated chromosome in actively dividing cells. Telomerase expression is not detected in terminally differentiated cells but is noticeable in 90% of the cancer cells. hTERT (human telomerase reverse transcriptase) expression seems to promote invasiveness of cancer cells. We here present proteomic profiles of cells overexpressing or knocked down for hTERT. This study also attempts to find out the potential interacting partners of hTERT in cancer cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28702647/an-enhanced-htert-promoter-driven-crispr-cas9-system-selectively-inhibits-the-progression-of-bladder-cancer-cells
#9
Xinbo Huang, Chengle Zhuang, Changshui Zhuang, Tiefu Xiong, Yawen Li, Yaoting Gui
The current therapies for treating tumors are lacking in efficacy and specificity. Synthetic biology principles may bring some new possible methods for curing cancer. Here we present a synthetic logic circuit based on the CRISPR/Cas9 system. The CRISPR/Cas9 technology has been applied in many biological fields, including cancer research. In this study, the expression of Cas9 nuclease was controlled indirectly by an enhanced hTERT promoter using the GAL4/upstream activating sequence (UAS) binding system. Cas9 was driven by 5XUAS, single guide RNA (sgRNA) was used to target mutant or wild-type HRAS, and the fusion gene GAL4-P65 was driven by the enhanced hTERT promoter...
July 12, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28700353/chiral-platinum-ii-4-2-3-dihydroxypropyl-formamide-oxo-aporphine-foa-complexes-promote-tumor-cells-apoptosis-by-directly-targeting-g-quadruplex-dna-in-vitro-and-in-vivo
#10
Qi-Pin Qin, Jiao-Lan Qin, Ming Chen, Yu-Lan Li, Ting Meng, Jie Zhou, Hong Liang, Zhen-Feng Chen
Three platinum(II) complexes, 4 (LC-004), 5 (LC-005), and 6 (LC-006), with the chiral FOA ligands R/S-(±)-FOA (1), R-(+)-FOA (2) and S-(-)-FOA (3), respectively, were synthesized and characterized. As potential anti-tumor agents, these complexes show higher cytotoxicity to BEL-7404 cells than the HL-7702 normal cells. They are potential telomerase inhibitors that target c-myc and human telomeric G-quadruplex DNA. Compared to complexes 4 and 5, 6 exhibited higher binding affinities towards telomeric, c-myc G-quadruplex DNA and caspase-3/9, thereby inducing senescence and apoptosis to a greater extent in tumor cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700015/telomere-length-and-htert-in-mania-and-subsequent-remission
#11
Rugül Köse Çinar
Objective: The findings of telomere length (TL) studies in bipolar disorder (BD) are controversial. The aim of the present study was to detect TL, human telomerase reverse transcriptase (hTERT), and brain derived neurotrophic factor (BDNF) in severe mania and subsequent remission. Methods: Twenty-one medication-free male patients and 20 age and gender matched controls were recruited. The patients were followed in the inpatient clinic, and comparisons were made between the same patients in their remission state and controls...
July 6, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/28698863/evaluation-of-the-expression-of-the-inhibitor-of-apoptosis-protein-family-and-human-telomerase-reverse-transcriptase-in-patients-with-advanced-colorectal-adenoma
#12
Joon Young Choi, Hyuk Yoon, Gyeongjae Na, Yoon Jin Choi, Cheol Min Shin, Young Soo Park, Nayoung Kim, Dong Ho Lee
BACKGROUND: It has been reported that the expression of the inhibitor of apoptosis protein (IAP) family increases in patients with colon cancer. We evaluated the expression of the IAP family and human telomerase reverse transcriptase (hTERT) in normal colon mucosa from patients with advanced colorectal adenoma and investigated their features according to characteristics of advanced colorectal adenoma. METHODS: While resections of polyps were performed in patients (n = 80) diagnosed with advanced colorectal adenoma or carcinoma in situ, additional normal tissues were obtained from the sigmoid colon...
June 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28698524/telomerase-induction-in-hpv-infection-and-oncogenesis
#13
REVIEW
Rachel Katzenellenbogen
Telomerase extends the repetitive DNA at the ends of linear chromosomes, and it is normally active in stem cells. When expressed in somatic diploid cells, it can lead to cellular immortalization. Human papillomaviruses (HPVs) are associated with and high-risk for cancer activate telomerase through the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT). The expression of hTERT is affected by both high-risk HPVs, E6 and E7. Seminal studies over the last two decades have identified the transcriptional, epigenetic, and post-transcriptional roles high-risk E6 and E7 have in telomerase induction...
July 10, 2017: Viruses
https://www.readbyqxmd.com/read/28693532/joint-quantitative-measurement-of-htert-mrna-in-both-peripheral-blood-and-circulating-tumor-cells-of-patients-with-nasopharyngeal-carcinoma-and-its-clinical-significance
#14
Xinsa Fu, Congxiang Shen, Huigang Wang, Fang Chen, Guanxue Li, Zhong Wen
BACKGROUND: The study was aimed to quantitatively detect mRNA levels of the catalytic subunit of telomerase (hTERT) in both peripheral blood and circulating tumor cells (CTCs) of patients with nasopharyngeal carcinoma (NPC) and explore its significance in early diagnosis and treatment of NPC. METHODS: hTERT mRNA levels in peripheral blood and CTCs of 33 NPC patients before and after treatment with intensity-modulated radiation therapy (IMRT) or/and chemotherapy and 24 healthy controls were measured using real-time quantitative PCR (qPCR) and their correlations to clinic pathological factors of NPC were analyzed...
July 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28693271/expression-of-tumor-suppressor-reic-dkk-3-by-a-newly-improved-adenovirus-vector-with-insertion-of-a-htert-promoter-at-the-3-side-of-the-transgene
#15
Endy Widya Putranto, Rie Kinoshita, Masami Watanabe, Takuya Sadahira, Hitoshi Murata, Ken-Ichi Yamamoto, Junichiro Futami, Ken Kataoka, Yusuke Inoue, I Made Winarsa Ruma, I Wayan Sumardika, Chen Youyi, Miyoko Kubo, Yoshihiko Sakaguchi, Kenji Saito, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh, Masakiyo Sakaguchi
Reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3) overexpression, induced using an adenovirus (Ad)-REIC, has been revealed to have a dramatic therapeutic effect on multiple types of cancer. To achieve an improved therapeutic effect from Ad-REIC on cancer, our group previously developed an enhanced gene expression system, the C-TSC cassette [cytomegalovirus (CMV)-RU5' located upstream (C); another promoter unit composed of triple tandem promoters, human telomerase reverse transcriptase (hTERT), simian virus 40 and CMV, located downstream of the cDNA (TSC); plus a polyadenylation (polyA) signal]...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28693240/melanoma-antigen-encoding-gene-family-member-a1-6-and-htert-in-the-detection-of-circulating-tumor-cells-following-cd45-depletion-and-rna-extraction
#16
Dae-Dong Kim, Chun-Seok Yang, Hyun-Dong Chae, Sang-Gyu Kwak, Chang-Ho Jeon
A total of 76 blood samples from patients without malignant disease and 107 blood samples from patients with malignant disease were investigated for the presence of circulating tumor cells (CTCs). To detect CTCs, hematopoietic cells were removed from the blood samples and different RNA extraction methods were used to amplify the melanoma antigen-encoding gene family member A1-family member A6 (MAGE A1-6) and the human telomerase reverse transcriptase (hTERT) gene as potential CTC markers. Comparison between four methods for extracting RNA from the blood was performed...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28691691/development-of-a-clay-based-bioink-for-3d-cell-printing-for-skeletal-application
#17
Tilman Ahlfeld, Gianluca Cidonio, David Kilian, Sarah Duin, Ashwini Rahul Akkineni, Jon I Dawson, Shoufeng Yang, Anja Lode, Richard Oreffo, Michael Gelinsky
Three-dimensional printing of cell-laden hydrogels has evolved as a promising approach on the route to patient-specific or complex tissue engineered constructs. However, it is still challenging to print structures with both, high shape fidelity and cell vitality. Herein, we used a synthetic nanosilicate clay, called Laponite, to build up scaffolds utilizing the extrusion-based method 3D plotting. By blending with alginate and methylcellulose, a bioink was developed which allowed easy extrusion, achieving scaffolds with high printing fidelity...
July 10, 2017: Biofabrication
https://www.readbyqxmd.com/read/28685587/3-dimensional-nano-fibre-scaffold-for-ex-vivo-expansion-of-cord-blood-haematopoietic-stem-cells
#18
Seyed Hadi Mousavi, Saeid Abroun, Masoud Soleimani, Seyed Javad Mowla
Cord blood (CB) haematopoietic stem cell (HSC) is an alternative source of HSC transplantation. The limited cell number greatly restricts their clinic-scale therapeutic applications. The objective of this study was an ex vivo expansion of CB HSCs in a new three-dimensional polycaprolactone nano-scaffold coated with fibronectin (FN). First, we isolated CB CD34+ cells and cultured 10 days in presence of growth factors. The evaluation was performed by qRT-PCR, flow cytometry and clonogenicity. 3D PCL nano-scaffold coated with FN produced significantly higher total nucleated cells and CD34+ cells (p < ...
July 7, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28679326/alternative-splicing-of-htert-a-further-mechanism-for-the-control-of-active-htert-in-acute-myeloid-leukemia
#19
Celeste Calvello, Barbara Rocca, Catherine Klersy, Rita Zappatore, Ilaria Giardini, Irene Dambruoso, Francesca Pasi, Marilena Caresana, Patrizia Zappasodi, Rosanna Nano, Marina Boni, Paolo Bernasconi
hTERT component is the key regulator of telomerase. Alternatively spliced variants of hTERT generate different telomerase activity. The goal of the study was to determine the role of different hTERT isoforms in the regulation of telomerase expression in AML patients. Among the 97 studied patients, 45 had a complex karyotype and 52 a normal karyotype. hTERT isoforms expression was determined in bone marrow samples by q-RT-PCR, using SYBR Green I. hTERT expression was lower in AML patients than controls (median 2...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28678551/nano-encapsulated-metformin-curcumin-in-plga-peg-inhibits-synergistically-growth-and-htert-gene-expression-in-human-breast-cancer-cells
#20
Raana Farajzadeh, Younes Pilehvar-Soltanahmadi, Mehdi Dadashpour, Shahrzad Javidfar, Javid Lotfi-Attari, Hadi Sadeghzadeh, Vahid Shafiei-Irannejad, Nosratollah Zarghami
The study was aimed at investigating the synergistic inhibitory effect of unique combinational regimen of nanocapsulated Metformin (Met) and Curcumin (Cur) against T47D breast cancer cells. For this purpose, Met and Cur were co-encapsulated in PEGylated PLGA nanoparticles (NPs) and evaluated for their therapeutic efficacy. The morphology and dynamic light scattering (DLS) analyses were carried out to optimize the nanoformulations. Drug release study was performed using dialysis method and then the cytotoxic and inhibitory effect of individual and combined drugs on expression level of hTERT in T47D breast cell line were evaluated using MTT assay and qPCR, respectively...
July 5, 2017: Artificial Cells, Nanomedicine, and Biotechnology
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