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Jinglong Zhang, Hongxia Cao, Jing Xie, Chen Fan, Youlong Xie, Xin He, Mingzhi Liao, Shiqiang Zhang, Huayan Wang
Unipotent spermatogonial stem cells (SSCs) can be efficiently reprogrammed into pluripotent stem cells only by manipulating the culture condition, without introducing exogenous reprogramming factors. This phenotype raises the hypothesis that the endogenous transcription factors (TFs) in SSCs may facilitate reprogramming to acquire pluripotency. In this study, we screened a pool of SSCs TFs (Bcl6b, Lhx1, Foxo1, Plzf, Id4, Taf4b, and Etv5), and found that oncogene Etv5 could dramatically increase the efficiency of induced pluripotent stem cells (iPSCs) generation when combined with Yamanaka factors...
February 14, 2018: Cell Death & Disease
Stephen J O'Brien, Jane V Carter, James F Burton, Brent G Oxford, Miranda N Schmidt, Jacob C Hallion, Susan Galandiuk
Colorectal cancer is associated with significant morbidity and mortality as many patients are diagnosed with advanced stage disease. MicroRNAs are small, non-coding RNA molecules which have a major role in gene expression regulation and are dysregulated in colorectal cancer. The miR-200 family is involved in epithelial-to-mesenchymal transition (EMT). This systematic review describes the roles of the miR-200 family in EMT in colorectal cancer. A search of electronic databases (PubMed and Embase) was conducted between January 2000 and July 2017...
January 31, 2018: International Journal of Cancer. Journal International du Cancer
Francesca Balzano, Sara Cruciani, Valentina Basoli, Sara Santaniello, Federica Facchin, Carlo Ventura, Margherita Maioli
In this review, we described different factors that modulate pluripotency in stem cells, in particular we aimed at following the steps of two large families of miRNAs: the miR-200 family and the miR-302 family. We analyzed some factors tuning stem cells behavior as TGF-β, which plays a pivotal role in pluripotency inhibition together with specific miRNAs, reactive oxygen species (ROS), but also hypoxia, and physical stimuli, such as ad hoc conveyed electromagnetic fields. TGF-β plays a crucial role in the suppression of pluripotency thus influencing the achievement of a specific phenotype...
January 30, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
S M Frisch, J C Farris, P M Pifer
The mammalian homologs of the D. melanogaster Grainyhead gene, Grainyhead-like 1-3 (GRHL1, GRHL2 and GRHL3), are transcription factors implicated in wound healing, tubulogenesis and cancer. Their induced target genes encode diverse epithelial cell adhesion molecules, while mesenchymal genes involved in cell migration and invasion are repressed. Moreover, GRHL2 suppresses the oncogenic epithelial-mesencyhmal transition, thereby acting as a tumor suppressor. Mechanisms, some involving established cancer-related signaling/transcription factor pathways (for example, Wnt, TGF-β, mir200, ZEB1, OVOL2, p63 and p300) and translational implications of the Grainyhead proteins in cancer are discussed in this review article...
November 2, 2017: Oncogene
Ellis Patrick, Sathyapriya Rajagopal, Hon-Kit Andus Wong, Cristin McCabe, Jishu Xu, Anna Tang, Selina H Imboywa, Julie A Schneider, Nathalie Pochet, Anna M Krichevsky, Lori B Chibnik, David A Bennett, Philip L De Jager
BACKGROUND: Given multiple studies of brain microRNA (miRNA) in relation to Alzheimer's disease (AD) with few consistent results and the heterogeneity of this disease, the objective of this study was to explore their mechanism by evaluating their relation to different elements of Alzheimer's disease pathology, confounding factors and mRNA expression data from the same subjects in the same brain region. METHODS: We report analyses of expression profiling of miRNA (n = 700 subjects) and lincRNA (n = 540 subjects) from the dorsolateral prefrontal cortex of individuals participating in two longitudinal cohort studies of aging...
July 1, 2017: Molecular Neurodegeneration
Minal Garg
Cancer metastasis occurs through local invasion of circulating tumour cells (CTCs), intravasation, transportation to distant sites, and their extravasation followed by colonisation at secondary sites. Epithelial-mesenchymal transition (EMT) is a normal developmental phenomenon, but its aberrant activation confers tumour cells with enhanced cell motility, metastatic properties, resistant to therapies and cancer stem cell (CSC) phenotype in epithelium-derived carcinoma. Experimental studies from various research papers have been reviewed to determine the factors, which interlink cancer stemness and cellular plasticity with EMT...
March 21, 2017: Expert Reviews in Molecular Medicine
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignacio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
April 25, 2017: Oncotarget
Jue Wang, Youli Zhang, Hong Wei, Xingxing Zhang, Yan Wu, Aihua Gong, Yu Xia, Wenbing Wang, Min Xu
Pancreatic cancer (PC) is a highly lethal disease due to extensive metastatic lesions. Accumulating evidence suggests that miR-675-5p plays different roles in metastasis through the regulation of epithelial to mesenchymal (EMT) and the mesenchymal to epithelial transitions (MET) in different cancers. ZEB1 promotes the EMT process by controlling the expression of E-cadherin and may have a reciprocal regulation with Ubiquilin1 (UBQLN1) and mir-200 family in cancer progression. In the present study, we showed that decreased expression of miR-675-5p is associated with the enhanced cell proliferation and survival of PC cells, while the increased expression of mir-675-5p shows the opposite one...
April 11, 2017: Oncotarget
Muhammad Zaeem Noman, Bassam Janji, Abderemane Abdou, Meriem Hasmim, Stéphane Terry, Tuan Zea Tan, Fathia Mami-Chouaib, Jean Paul Thiery, Salem Chouaib
PD-L1 expression and regulation by mesenchymal tumor cells remain largely undefined. Here, we report that among different EMT-activated MCF7 human breast cancer cell clones, PD-L1 was differentially upregulated in MCF7 sh-WISP2, MCF7-1001/2101, and MDA-MB-231 cells but not in MCF7 SNAI1 and MCF7 SNAI1-6SA cells. Mechanistic investigations revealed that siRNA silencing of ZEB-1, but not SNAI1, TWIST, or SLUG and overexpression of miR200 family members in MCF7 sh-WISP2 cells strongly decreased PD-L1 expression...
2017: Oncoimmunology
Jing Li, Xiaoyun Xing, Daofeng Li, Bo Zhang, David G Mutch, Ian S Hagemann, Ting Wang
Uterine carcinosarcoma (UCS) is a form of endometrial cancer simultaneously exhibiting carcinomatous and sarcomatous elements, but the underlying molecular and epigenetic basis of this disease is poorly understood. We generated complete DNA methylomes for both the carcinomatous and the sarcomatous components of three UCS samples separated by laser capture microdissection and compared DNA methylomes of UCS with those of normal endometrium as well as methylomes derived from endometrioid carcinoma, serous endometrial carcinoma, and endometrial stromal sarcoma...
February 2017: Neoplasia: An International Journal for Oncology Research
Romana Urbas, Christian Mayr, Eckhard Klieser, Julia Fuereder, Doris Bach, Stefan Stättner, Florian Primavesi, Tarkan Jaeger, Stefanie Stanzer, Anna Lena Ress, Magdalena Löffelberger, Andrej Wagner, Frieder Berr, Markus Ritter, Martin Pichler, Daniel Neureiter, Tobias Kiesslich
Extensive stromal interaction is one reason for the dismal outcome of biliary tract cancer (BTC) patients. Epithelial to mesenchymal transition (EMT) is involved in tumor invasion and metastasis and is partly regulated by microRNAs (miRs). This study explores the expression of anti-EMT miR200 family (miR141, -200a/b/c, -429) and miR205 as well as the EMT-related proteins E-cadherin and vimentin in a panel of BTC cell lines and clinical specimens by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry, respectively...
December 7, 2016: International Journal of Molecular Sciences
Silvio Holzner, Daniel Senfter, Serena Stadler, Anna Staribacher, Chi Huu Nguyen, Anna Gaggl, Silvana Geleff, Nicole Huttary, Sigurd Krieger, Walter Jäger, Helmut Dolznig, Robert M Mader, Georg Krupitza
Since cancer cells, when grown as spheroids, display drug sensitivity and radiation resistance patterns such as seen in vivo we recently established a three‑dimensional (3D) in vitro model recapitulating colorectal cancer (CRC)-triggered lymphatic endothelial cell (LEC)‑barrier breaching to study mechanisms of intra‑/extravasation. CRC metastasizes not only through lymphatics but also through blood vessels and here we extend the 3D model to the interaction of blood endothelial cells (BECs) with naïve and 5‑fluorouracil (5‑FU)‑resistant CRC CCL227 cells...
November 2016: Oncology Reports
Rajendra Narayan Mitra, Chance A Nichols, Junjing Guo, Rasha Makkia, Mark J Cooper, Muna I Naash, Zongchao Han
We recently reported that the Ins2(Akita) mouse is a good model for late-onset diabetic retinopathy. Here, we investigated the effect of miR200-b, a potential anti-angiogenic factor, on VEGF receptor 2 (VEGFR-2) expression and to determine the underlying angiogenic response in mouse endothelial cells, and in retinas from aged Ins2(Akita) mice. MiR200-b and its native flanking sequences were amplified and cloned into a pCAG-eGFP vector directed by the ubiquitous CAG promoter (namely pCAG-miR200-b-IRES-eGFP)...
August 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Pui-Wah Choi, Junzheng Yang, Shu-Kay Ng, Colleen Feltmate, Michael G Muto, Kathleen Hasselblatt, Kyle Lafferty-Whyte, Lellean JeBailey, Laura MacConaill, William R Welch, Wing-Ping Fong, Ross S Berkowitz, Shu-Wing Ng
Increased inclusion cyst formation in the ovary is associated with ovarian cancer development. We employed in vitro three-dimensional (3D) organotypic models formed by normal human ovarian surface epithelial (OSE) cells and ovarian cancer cells to study the morphologies of normal and cancerous ovarian cortical inclusion cysts and the molecular changes during their transitions into stromal microenvironment. When compared with normal cysts that expressed tenascin, the cancerous cysts expressed high levels of laminin V and demonstrated polarized structures in Matrigel; and the cancer cells migrated collectively when the cyst structures were positioned in a stromal-like collagen I matrix...
January 26, 2016: Oncotarget
Shweta Bhatt, Manoj K Gupta, Mogher Khamaisi, Rachael Martinez, Marina A Gritsenko, Bridget K Wagner, Patrick Guye, Volker Busskamp, Jun Shirakawa, Gongxiong Wu, Chong Wee Liew, Therese R Clauss, Ivan Valdez, Abdelfattah El Ouaamari, Ercument Dirice, Tomozumi Takatani, Hillary A Keenan, Richard D Smith, George Church, Ron Weiss, Amy J Wagers, Wei-Jun Qian, George L King, Rohit N Kulkarni
The mechanisms underlying the development of complications in type 1 diabetes (T1D) are poorly understood. Disease modeling of induced pluripotent stem cells (iPSCs) from patients with longstanding T1D (disease duration ≥ 50 years) with severe (Medalist +C) or absent to mild complications (Medalist -C) revealed impaired growth, reprogramming, and differentiation in Medalist +C. Genomics and proteomics analyses suggested differential regulation of DNA damage checkpoint proteins favoring protection from cellular apoptosis in Medalist -C...
August 4, 2015: Cell Metabolism
Shiv K Singh, Nai-Ming Chen, Elisabeth Hessmann, Jens Siveke, Marlen Lahmann, Garima Singh, Nadine Voelker, Sophia Vogt, Irene Esposito, Ansgar Schmidt, Cornelia Brendel, Thorsten Stiewe, Jochen Gaedcke, Marco Mernberger, Howard C Crawford, William R Bamlet, Jin-San Zhang, Xiao-Kun Li, Thomas C Smyrk, Daniel D Billadeau, Matthias Hebrok, Albrecht Neesse, Alexander Koenig, Volker Ellenrieder
In adaptation to oncogenic signals, pancreatic ductal adenocarcinoma (PDAC) cells undergo epithelial-mesenchymal transition (EMT), a process combining tumor cell dedifferentiation with acquisition of stemness features. However, the mechanisms linking oncogene-induced signaling pathways with EMT and stemness remain largely elusive. Here, we uncover the inflammation-induced transcription factor NFATc1 as a central regulator of pancreatic cancer cell plasticity. In particular, we show that NFATc1 drives EMT reprogramming and maintains pancreatic cancer cells in a stem cell-like state through Sox2-dependent transcription of EMT and stemness factors...
February 12, 2015: EMBO Journal
Xiaofeng Xue, Ye Zhang, Qiaoming Zhi, Min Tu, Yue Xu, Jie Sun, Jishu Wei, Zipeng Lu, Yi Miao, Wentao Gao
BACKGROUND: Hepatocellular carcinoma (HCC) typically relies on tumor transformation and angiogenesis for its malignant behavior, including growth and metastasis. Previously, we reported that Vasohibin2 (VASH2) is preferentially expressed in hepatocellular carcinoma (HCC) tumor tissues and promotes angiogenesis. Here, we further investigated the role of VASH2 in HCC tumor progression. RESULTS: Bioinformatics analyses and luciferase reporter gene assays confirmed the post-transcriptional regulation of VASH2 by miR-200a/b/c...
2014: Cell Communication and Signaling: CCS
Mingyang Lu, Mohit Kumar Jolly, Jose' Onuchic, Eshel Ben-Jacob
Understanding epithelial-mesenchymal transitions (EMT) during cancer metastasis remains a major challenge in modern biology. Recent observations of cell behavior together with progress in mapping the underlying regulatory genetic networks led to new understandings of carcinoma metastasis. It is now established that the genetic network that regulates the EMT also enables an epithelial-mesenchymal hybrid phenotype. These hybrid cells possess mixed carcinoma epithelial and mesenchymal characteristics that enable specialized capabilities such as collective cell migration...
September 1, 2014: Cancer Research
Karen H Hales, Sheree C Speckman, Nawneet K Kurrey, Dale B Hales
BACKGROUND: The laying hen model of spontaneous epithelial ovarian cancer (EOC) is unique in that it is the only model that enables observations of early events in disease progression and is therefore also uniquely suited for chemoprevention trials. Previous studies on the effect of dietary flaxseed in laying hens have revealed the potential for both amelioration and prevention of ovarian cancer. The objective of this study was to assess the effect of flaxseed on genes and pathways that are dysregulated in tumors...
2014: BMC Genomics
Ningxia Sun, Qing Zhang, Chen Xu, Qian Zhao, Yan Ma, Xinmei Lu, Liang Wang, Wen Li
The molecular mechanism underlying ovarian cancer invasiveness and metastasis remains unclear. Since significant downregulation in microRNA 200 (miRNA200) family (miR200a, miR200b, and miR200c) has been reported in the invasive ovarian cancer cells, here, we used two human ovarian cancer cell lines, OVCAR3 and SKOV3, to study the molecular basis of miR200, matrix metalloproteinase 3 (MMP3) activation, and cancer invasiveness. We found that overexpression of either miR200 family member in OVCAR3 or SKOV3 cells significantly inhibited production and secretion of MMP3 and cancer invasiveness...
November 2014: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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